The Hallmarks of Cancer: 8 - Tumor-Promoting InflammationAfter a too-long hiatus, here is my eighth article in this series :) The Hallmarks of Cancer are ten anti-cancer defense mechanisms that are hardwired into our cells, that must be breached by a cell on the path towards cancer. The Eighth Hallmark of Cancer is defined as “Tumor-Promoting Inflammation”. All seven previous Hallmark articles can be found here: http://goo.gl/IDGfLpAs always, because this is such a complex topic, I don’t want to skip details at the cost of avoiding TL;DR. So I’ve written a far more detailed explanation (complete with my own diagrams!) that is easier to follow on +Scientific American, and I highly recommend you check it out here: http://goo.gl/ThMpl9. In this article, I explain the complex relationship between inflammation and cancer, and how our own immune system can ‘turn traitor’ and promote cancer development.✤ Within the last few years, we have obtained clear evidence that inflammation plays a critical role in cancer development, and we are just beginning to understand the molecular mechanisms of how this happens. Chronic infections, obesity, smoking, alcohol consumption, environmental pollutants and high fat diets are now recognized as major risk factors for most common types of cancer; and, importantly, all these risk factors are linked to cancer through inflammation. ✤ Inflammation is how tissues and cells respond to injury. If the inflammation causing agent persists for a prolonged period of time, the body’s response to it becomes a chronic inflammation. Chronic inflammation increases cancer risk. ✤ An extremely graphic yet apt way of describing a tumor is as “a wound that doesn’t heal”. Indeed, there are many similarities between a cancerous tumor and the process of wound healing. Both involve the growth, survival, and migration of cells; both require the growth of new blood vessels; importantly, all these processes are controlled by growth factors and signalling molecules. Just as the immune cells gather near a site of injury to secrete growth factors to begin tissue repair, tumors can also surround themselves with immune cells that secrete these same growth factors to promote their uncontrolled cell growth. ✤ Tumor Associated Macrophages (TAMs), a ‘corrupted’ type of immune cell support tumors in four different ways; by providing growth factors, helping to develop a blood supply to the tumor, promoting metastasis and suppressing the tumor-killing abilities of the immune system. Essentially, TAMs help the tumor overcome the barriers represented by the anti-cancer defence mechanisms that consist the Hallmarks. ✤ The existence of both tumor-promoting and tumor-killing immune cells at first seems counter-intuitive. The immune cells specializing in wound cleaning and clearing up dead cells are recruited and subverted by tumor cells to support tumor growth and progression. Shifting the balance from tumor-promoting to tumor-killing immune involvement therefore represents an attractive and powerful possibility for future therapy.  #ScienceSunday    #ScienceEveryday   #HallmarksOfCancerhttp://click-to-read-mo.re/p/6G8X

The Hallmarks of Cancer: 8 - Tumor-Promoting Inflammation

After a too-long hiatus, here is my eighth article in this series :) The Hallmarks of Cancer are ten anti-cancer defense mechanisms that are hardwired into our cells, that must be breached by a cell on the path towards cancer. The Eighth Hallmark of Cancer is defined as “Tumor-Promoting Inflammation”. All seven previous Hallmark articles can be found here: http://goo.gl/IDGfLp

As always, because this is such a complex topic, I don’t want to skip details at the cost of avoiding TL;DR. So I’ve written a far more detailed explanation (complete with my own diagrams!) that is easier to follow on +Scientific American, and I highly recommend you check it out here: http://goo.gl/ThMpl9. In this article, I explain the complex relationship between inflammation and cancer, and how our own immune system can ‘turn traitor’ and promote cancer development.

✤ Within the last few years, we have obtained clear evidence that inflammation plays a critical role in cancer development, and we are just beginning to understand the molecular mechanisms of how this happens. Chronic infections, obesity, smoking, alcohol consumption, environmental pollutants and high fat diets are now recognized as major risk factors for most common types of cancer; and, importantly, all these risk factors are linked to cancer through inflammation. 

✤ Inflammation is how tissues and cells respond to injury. If the inflammation causing agent persists for a prolonged period of time, the body’s response to it becomes a chronic inflammation. Chronic inflammation increases cancer risk. 

✤ An extremely graphic yet apt way of describing a tumor is as “a wound that doesn’t heal”. Indeed, there are many similarities between a cancerous tumor and the process of wound healing. Both involve the growth, survival, and migration of cells; both require the growth of new blood vessels; importantly, all these processes are controlled by growth factors and signalling molecules. Just as the immune cells gather near a site of injury to secrete growth factors to begin tissue repair, tumors can also surround themselves with immune cells that secrete these same growth factors to promote their uncontrolled cell growth. 

✤ Tumor Associated Macrophages (TAMs), a ‘corrupted’ type of immune cell support tumors in four different ways; by providing growth factors, helping to develop a blood supply to the tumor, promoting metastasis and suppressing the tumor-killing abilities of the immune system. Essentially, TAMs help the tumor overcome the barriers represented by the anti-cancer defence mechanisms that consist the Hallmarks. 

✤ The existence of both tumor-promoting and tumor-killing immune cells at first seems counter-intuitive. The immune cells specializing in wound cleaning and clearing up dead cells are recruited and subverted by tumor cells to support tumor growth and progression. Shifting the balance from tumor-promoting to tumor-killing immune involvement therefore represents an attractive and powerful possibility for future therapy. 

#ScienceSunday   #ScienceEveryday   #HallmarksOfCancer

http://click-to-read-mo.re/p/6G8X

Monkey Planet

The Beeb has a wonderful new series featuring Professor George McGavin from the University of Oxford. Titled Monkey Planet, it describes the various species of primates that inhabit our planet. The footage is amazing, which isn’t a surprise given it’s a BBC Nature documentary. I think my favourite part so far was this behind-the-scenes clip of Bonobos. They are so adorably playful and boisterous!

If you have access to the BBC iPlayer (or ahem, a handy plugin that allows you to view UK content) this series is definitely worth checking out: http://www.bbc.co.uk/programmes/p01r52gr

+Erin Kane this might be of interest to you, if you haven’t seen it already!

#ScienceEveryday

http://click-to-read-mo.re/p/6whb

"Exploding Cancer Cells" ExplainedBy now many of you may have seen reports of a new ‘breakthrough’ in cancer research resulting in ‘exploding cancer cells’ (http://goo.gl/MT1j7z). These reports are in reference to a new study published in the journal Cell. What exactly does this mean, and how realistic is it to expect this treatment to reach patients anytime soon?✤ In this study, scientists focused on a very aggressive, essentially incurable type of brain cancer known as glioblastoma. Glioblastomas typically have a lot of things wrong with it, meaning most of our inherent hard-wired cellular defense mechanisms (http://goo.gl/fFw7xP) have been overridden. Even worse, glioblastomas tend to harbor a subset of cells known as ‘cancer stem cells’ that are resistant to treatment and can repopulate the tumor following treatment (http://goo.gl/qwHFOL).✤ The scientists screened a range of compounds for their ability to specifically kill glioblastoma cells in culture (i.e. grown in a petri dish). They identified a compound they named Vacquinol-1 which was highly specific; it had no effect on other types of cells, only glioblastoma cells.✤ Next, they were curious about the mechanism of cell death and discovered that the cells did not die through apoptosis, i.e. the cell suicide program. However they did find that the cell membranes rapidly changed their shape when treated with Vacquinol-1, indicating that the process had something to do with endocytosis.✤ Endocytosis is a process by which small molecules are brought into the cell from the outside. The cell membrane forms an invagination (crater-like cups), and the molecules are enclosed in a vesicle (a small bubble) within the cell. When glioblastoma cells were treated with Vacquinol-1, they observed the rapid rounding of cells, the formation of spherical protrusions and irregular bulging of the cell membrane, followed by eventual rupture of the cells through a necrotic-like cell death mechanism. This is the part that has been likened to ‘exploding cells’.✤ Next, in order to fully understand the cellular signalling mechanisms involved, they looked at which genes are involved in this process of cell rupture. They identified a gene known as MKK4 which is involved in many cellular processes such as growth, inflammation and apoptosis. Although the exact mechanism of this pathway is yet to be identified, when MKK4 is missing, Vacquinol-1 had no effect on the cells, indicating that the MKK4 gene is required for this process.✤ All this was done in petri-dishes so next they tested Vacquinol-1 on mice that had glioblastomas and found that the compound significantly reduced the size of the tumors. The mice in the control group had a median survival (i.e. half the mice were dead) of 31.5 days. In contrast, only two of the eight Vacquinol-1-treated mice died during the 80 days of the experiment. Clearly, the compound had a very pronounced effect on survival.✤ Clearly there is a long way to go with this work, which is very promising. But it is important to remember that this has only been done in a petri-dish and in mice. It hasn’t been tested in humans. Pre-clinical trials are a while away yet, and while it is tempting to get excited about the idea of ‘exploding cancer cells’, a degree of caution is a must.Further readingOriginal research paper: http://goo.gl/74CXOPImage: Mouse brain treated with control (left) or Vacquinol-1 (right). Notice the significantly smaller tumor upon treatment with Vacquinol-1.H/T +Adam Gill for pinging me on this! #ScienceEveryday     #ScienceMediaHypehttp://click-to-read-mo.re/p/6fpf

"Exploding Cancer Cells" Explained

By now many of you may have seen reports of a new ‘breakthrough’ in cancer research resulting in ‘exploding cancer cells’ (http://goo.gl/MT1j7z). These reports are in reference to a new study published in the journal Cell. What exactly does this mean, and how realistic is it to expect this treatment to reach patients anytime soon?

✤ In this study, scientists focused on a very aggressive, essentially incurable type of brain cancer known as glioblastoma. Glioblastomas typically have a lot of things wrong with it, meaning most of our inherent hard-wired cellular defense mechanisms (http://goo.gl/fFw7xP) have been overridden. Even worse, glioblastomas tend to harbor a subset of cells known as ‘cancer stem cells’ that are resistant to treatment and can repopulate the tumor following treatment (http://goo.gl/qwHFOL).

✤ The scientists screened a range of compounds for their ability to specifically kill glioblastoma cells in culture (i.e. grown in a petri dish). They identified a compound they named Vacquinol-1 which was highly specific; it had no effect on other types of cells, only glioblastoma cells.

✤ Next, they were curious about the mechanism of cell death and discovered that the cells did not die through apoptosis, i.e. the cell suicide program. However they did find that the cell membranes rapidly changed their shape when treated with Vacquinol-1, indicating that the process had something to do with endocytosis.

✤ Endocytosis is a process by which small molecules are brought into the cell from the outside. The cell membrane forms an invagination (crater-like cups), and the molecules are enclosed in a vesicle (a small bubble) within the cell. When glioblastoma cells were treated with Vacquinol-1, they observed the rapid rounding of cells, the formation of spherical protrusions and irregular bulging of the cell membrane, followed by eventual rupture of the cells through a necrotic-like cell death mechanism. This is the part that has been likened to ‘exploding cells’.

✤ Next, in order to fully understand the cellular signalling mechanisms involved, they looked at which genes are involved in this process of cell rupture. They identified a gene known as MKK4 which is involved in many cellular processes such as growth, inflammation and apoptosis. Although the exact mechanism of this pathway is yet to be identified, when MKK4 is missing, Vacquinol-1 had no effect on the cells, indicating that the MKK4 gene is required for this process.

✤ All this was done in petri-dishes so next they tested Vacquinol-1 on mice that had glioblastomas and found that the compound significantly reduced the size of the tumors. The mice in the control group had a median survival (i.e. half the mice were dead) of 31.5 days. In contrast, only two of the eight Vacquinol-1-treated mice died during the 80 days of the experiment. Clearly, the compound had a very pronounced effect on survival.

✤ Clearly there is a long way to go with this work, which is very promising. But it is important to remember that this has only been done in a petri-dish and in mice. It hasn’t been tested in humans. Pre-clinical trials are a while away yet, and while it is tempting to get excited about the idea of ‘exploding cancer cells’, a degree of caution is a must.

Further reading
Original research paper: http://goo.gl/74CXOP
Image: Mouse brain treated with control (left) or Vacquinol-1 (right). Notice the significantly smaller tumor upon treatment with Vacquinol-1.

H/T +Adam Gill for pinging me on this!

#ScienceEveryday    #ScienceMediaHype

http://click-to-read-mo.re/p/6fpf

Cancer Signalling HOA

We’re just getting set up and will be going live in about 30 minutes time. Hope you can join me as I interview +Akinola Emmanuel and +shilpa keerthivasan on their recently published research on the Wnt Signalling pathway.

#ScienceSunday

▼ Reshared Post From Science on Google+ ▼

Join us for a Science on Google+ HOA as we speak to +Akinola Emmanuel and Dr +shilpa keerthivasan about their recently published research on cancer signalling (http://stm.sciencemag.org/content/6/225/225ra28). We will discuss the basics of cancer signalling, explain the link between inflammation and cancer, and how their research identifies a novel role for immune cells in the development of colon cancer. This Pub Talks HOA will be part of a series in which we explain published research in a jargon-free manner that is understandable to the public.

This HOA will be hosted by Dr +Buddhini Samarasinghe and you can tune in on Sunday March 23rd at 2 PM CDT/ 12PM PDT/ 7 PM GMT. The hangout will be available for viewing on our YouTube channel (https://www.youtube.com/ScienceHangouts) after the event.

http://click-to-read-mo.re/p/6dz2

Cancer Signalling: The Wnt PathwayWe are multi-cellular animals, and as such, our cells need to communicate with each other, so they can act in a coordinated manner in response to the environment. The basis of this communication comes from a process known as cell signalling. Various signalling molecules surrounding the cellular environment can stimulate cells to grow and divide at the appropriate time. When these carefully regulated cellular processes go wrong, cancer happens.✤ The Wnt Signalling Pathway (pronounced ‘wint’) is one of the most studied signalling pathways in molecular biology.  Discovered over thirty years ago, it is also a pathway that is frequently disrupted in cancer, particularly colon cancer. What is this pathway and how does it work?✤ In Wnt signalling, the key effector is a molecule known as beta catenin. Under normal circumstances (when Wnt signalling is not active) beta catenin is constantly made by the cell and constantly destroyed. A new molecule of beta catenin only lasts in the cell for about 5 minutes before it is destroyed. However when Wnt signalling is active, this destruction is halted, so that beta catenin accumulates within the cell. Once beta catenin levels reach a certain threshold, it moves into the nucleus, binds to DNA and activates other genes that go on to promote cell division.✤ One of the most common mutations in colon cancer is a gene known as APC. APC is part of the protein complex that destroys beta catenin. When APC is mutated, beta catenin cannot be destroyed; it accumulates in the cell and causes uncontrolled cell growth. It’s like a car with no brakes. It can lead to the development of hundreds of polyps in the colon as illustrated by the picture below. Although benign at first, these polyps can turn cancerous if left untreated. Unsurprisingly, people who have mutant APC have a nearly 100% chance of developing colon cancer by the age of 40 years.✤ What effect does beta catenin activation have on different cells in our body? What are the other components of the Wnt signalling pathway and are there other ways in which beta catenin levels can be regulated by the cell? Can we exploit our knowledge of this pathway to inhibit beta catenin, to develop therapies to treat colon cancer? These are all areas of ongoing research, and there are many exciting new developments in the field of Wnt signalling.On Sunday March 23, I will be speaking to +Akinola Emmanuel and +shilpa keerthivasan about their recently published research (http://goo.gl/BS2VH8) looking at Wnt signalling in immune cells. Their results are fascinating! You can RSVP to watch it here (http://goo.gl/QzeWAa), and the video will be available on YouTube after the event. For a great essay on the history of Wnt signalling, check out this review from the EMBO Journal (#openaccess) http://goo.gl/NE13yuIf you want to know more details on the mechanism of Wnt signalling, here’s a good video: The Wnt pathway in a normal and in a tumour cellImage credit: http://goo.gl/5utwfMhttp://click-to-read-mo.re/p/69DF

Cancer Signalling: The Wnt Pathway

We are multi-cellular animals, and as such, our cells need to communicate with each other, so they can act in a coordinated manner in response to the environment. The basis of this communication comes from a process known as cell signalling. Various signalling molecules surrounding the cellular environment can stimulate cells to grow and divide at the appropriate time. When these carefully regulated cellular processes go wrong, cancer happens.

✤ The Wnt Signalling Pathway (pronounced ‘wint’) is one of the most studied signalling pathways in molecular biology.  Discovered over thirty years ago, it is also a pathway that is frequently disrupted in cancer, particularly colon cancer. What is this pathway and how does it work?

✤ In Wnt signalling, the key effector is a molecule known as beta catenin. Under normal circumstances (when Wnt signalling is not active) beta catenin is constantly made by the cell and constantly destroyed. A new molecule of beta catenin only lasts in the cell for about 5 minutes before it is destroyed. However when Wnt signalling is active, this destruction is halted, so that beta catenin accumulates within the cell. Once beta catenin levels reach a certain threshold, it moves into the nucleus, binds to DNA and activates other genes that go on to promote cell division.

✤ One of the most common mutations in colon cancer is a gene known as APC. APC is part of the protein complex that destroys beta catenin. When APC is mutated, beta catenin cannot be destroyed; it accumulates in the cell and causes uncontrolled cell growth. It’s like a car with no brakes. It can lead to the development of hundreds of polyps in the colon as illustrated by the picture below. Although benign at first, these polyps can turn cancerous if left untreated. Unsurprisingly, people who have mutant APC have a nearly 100% chance of developing colon cancer by the age of 40 years.

✤ What effect does beta catenin activation have on different cells in our body? What are the other components of the Wnt signalling pathway and are there other ways in which beta catenin levels can be regulated by the cell? Can we exploit our knowledge of this pathway to inhibit beta catenin, to develop therapies to treat colon cancer? These are all areas of ongoing research, and there are many exciting new developments in the field of Wnt signalling.

On Sunday March 23, I will be speaking to +Akinola Emmanuel and +shilpa keerthivasan about their recently published research (http://goo.gl/BS2VH8) looking at Wnt signalling in immune cells. Their results are fascinating! You can RSVP to watch it here (http://goo.gl/QzeWAa), and the video will be available on YouTube after the event. 

For a great essay on the history of Wnt signalling, check out this review from the EMBO Journal (#openaccess) http://goo.gl/NE13yu

If you want to know more details on the mechanism of Wnt signalling, here’s a good video: The Wnt pathway in a normal and in a tumour cell

Image credit: http://goo.gl/5utwfM

http://click-to-read-mo.re/p/69DF