I am building a model of avascular tumour growth and an important question is can cells that are completely surrounded still divide and push out the outer cells. Models I've seen so far consider all surrounded cells quiescent, but it doesn't sound correct to me - cancer cells can push through surrounding tissues, why not their own "tissue"?
I suppose there may still be differences in the proliferation of inner/outer cells, thus the wording of the question.
Ivan
There is probably high difference in proliferation between the core and outer borders of a tumor. But the reason is more probably an issue of nutrient availability instead of being able to push. The cells in the core of a theoretical non-vascular tumor would have less access to nutrients and more accumulation of toxic metabolites. There is never an empty space at the first place where tumor develops, it always pushes out healthy tissue. The quiescence of surrounded cells can be true for healthy cells but One of the key markers of cancer is losing the ability to stop proliferating when it is surrounded. In other words loss of contact dependent inhibition. I hope I could give some ideas.
Interesting question that you have to address, e.g. by PCNA staining or (in an animal model) labeling in vivo with BrdU. We did a comparison for lung mets in a mouse model where we stained for PCNA and looked at small and large mets. You can see the blood vessels nicely and distinguish tumor from lung due to the unique structure of lung tissues. It turns out that there was no difference between regions staining with PCNA in small or large lestions. In contrast, when we stained for an indicator of cell density from the Hippo pathway, YAP, we found that nuclear location of that marker was very different depending on the tumor size.I copy a link below. The paper is Sharif et al, Oncogene 2015.
Thus, from this experiments cells in a tumor do "recognize" their position and respond accordingly; it does not seem to impact proliferation at least in this model [ Those were MDA-MB-231 cells grown in mice ].
Hope this helps - think you should do some PCNA stainings of a cancer you are interested in.
Anton
Sharif et al, Oncogene 2015:
https://www.dropbox.com/s/mbt5xwr7141u3t9/Sharif%20Cell%20growth%20density%20modulates%20cancer%20Oncogene%202015.pdf?dl=0
Anton Wellstein, MD PhD
Professor Oncology, Pharmacology and Medicine
Georgetown University Medical School
Associate Director for Basic Science
Lombardi Comprehensive Cancer Center
Research Building; Room E311
3970 Reservoir Road
Washington DC 20057-1469
+1 (202) 687-3672 phone
+1 (202) 687-4821 fax
Published papers: http://www.ncbi.nlm.nih.gov/myncbi/browse/collection/41166899/?sort=date&direction=descending
Lab website: https://sites.google.com/a/georgetown.edu/wellstein-lab-1/home/
Thank you both for the answers! This is a general computational model, so I am looking for the evidence basis of adding a proliferation function for core tumour cells. I am not aiming to model a specific type of cancer, the model should be able to provide the necessary tumour properties for a wide array of types.
- Badges
- Science topic
- Similar topics
- Medicine
- Oncology
- Cancer Research
- Cancer Biology
- Cancer Cells