The entire phenomenon of tumor dormancy demonstrates that proliferation and metastasis are uncoupled.

In many of the tumors we studied, particularly melanoma, and more dramatically eye melanomas at first, cells escape from the primary ocular tumor, and 80-90% of the time cause liver mets. Even when primaries are removed surgically completely, often times there are two peaks of recurrence: 11 years post-primary removal, and 21 years. Unless the cells that explode in the liver 11 or 21 years later constitute a new melanoma (which evidence suggest they are not but instead derive from the primary because of numerous marker characteristics, this good question must be resolved to the hypothesis that those mets were sleeping for 11 or 21 years, and then woke up and started proliferating again. This demonstrates that the two processes, invasion and metastasis are indeed uncoupled (in certain tumor syndromes. Folkman's concomitant resistance mouse models with Lewis Lung carcinoma are a similar example of dormancy, but with a twist....the primary in this case makes the lung mets sleep until it is removed. Then they expode. This suggests that the primary (secreting endostatin in the mouse) lulls the escaped (migrating) met cells non-proliferative, as they remain as micro-mets until the primary is removed from the mouse's back, or unless TGFB is injected near the lungs, or unless surgical disturbance wakes them up. I thought this was a very good question to consider. Thank you,.

Andrew Maniotis, PhD

Invasive cancer cells proliferate; they may not proliferte while actively moving (which they dont do all the time) and cells usually stop moving while dividing (which takes mnutes to an hour), but then they may migrate again. Of course, DNA synthesis and other prolifaration-related processes can go on dudring migration (invasion).

However, many gene promote (or inhibit) these two processes simultaneously. I don't know these processes are doordinated

Very interesting question but no ready answer yet. I guess a cancer cell must keep the ability to proliferate while (if) invading, and it must proactively proliferate after successful invasion. However it doesn't have to actually divide while migrating. The two processes may be mutually exclusive, as Nicole said, but only at some stage in a real-time sense. They are both needed by that very cell for successful colonization.

I think that this paper will be of your interest, take a look!

http://www.ncbi.nlm.nih.gov/pubmed/19713745

Reduced proliferation and enhanced migration: two sides of the same coin?

The changes that occur in the architecture of the cytoskeleton during proliferation are not compatable with those needed for migration/ invasion.

Thank you very much everybody for your valuable inputs ! Leon, you bring up a interesting point ! Do you known if actin polymerization is a required step during invasion / migration in cancer cells ?

Yes, actin-treadmilling generates the protrusive force for invadopodia.

Each neoplasm has a development with episodic periods of growth, regresion, differentiation and further bizare tumour specialization, which could occur rather not for whole tumour mass, than focally or on invasive front. One of the articles which elaborate scientific topic of your question, and highlight in its title the dillema from your question: "invade or proliferate", is Svensson's and coworkers: "Svensson S, Nilsson K, Ringberg A, Landberg G. Invade or proliferate? Two contrasting events in malignant behavior governed by p16(INK4a) and an intact Rb pathway illustrated by a model system of basal cell carcinoma. Cancer Res. 2003 Apr 15;63(8):1737-42." (http://www.ncbi.nlm.nih.gov/pubmed/12702553), and represents one part of puzzle, considering proliferation, and cell cycle control.

Very good question that could be asked to the proteomic anlyse !

This recently published paper supports the idea that invasion and proliferation are mutually exclusive in certain cellular models, highlighting dynamics in cell plasticity. Here you have the link of it: http://www.jci.org/articles/view/59218. Another previous paper already made similar suggestions: http://cancerres.aacrjournals.org/content/68/24/10377.long.

And this 2008 paper for melanoma: http://www.ncbi.nlm.nih.gov/pubmed/18245463

I think this question should be declared more clearly as: If cell sub-populations with higher invasion tendency proliferate slowly than other sub-populations?

I think there are the possibility that some cell sub- populations of a certain cancer could simultaneous have higher invasion ability and proliferation ability than other cell sub-populations of the same kind of cancer.

@ Xiaujin Liu. Proliferation and invasion are uncoupled. The rate of switching between both states is not only cell type dependent, but also regulated by environmental cues.

How do the expression and function of efflux and influx transporters change during proliferation and migration? Whether there is a difference in drug resistance?

Thank you everybody for your suggestions and the papers ! I found the papers very insightful !

The entire phenomenon of tumor dormancy demonstrates that proliferation and metastasis are uncoupled.

In many of the tumors we studied, particularly melanoma, and more dramatically eye melanomas at first, cells escape from the primary ocular tumor, and 80-90% of the time cause liver mets. Even when primaries are removed surgically completely, often times there are two peaks of recurrence: 11 years post-primary removal, and 21 years. Unless the cells that explode in the liver 11 or 21 years later constitute a new melanoma (which evidence suggest they are not but instead derive from the primary because of numerous marker characteristics, this good question must be resolved to the hypothesis that those mets were sleeping for 11 or 21 years, and then woke up and started proliferating again. This demonstrates that the two processes, invasion and metastasis are indeed uncoupled (in certain tumor syndromes. Folkman's concomitant resistance mouse models with Lewis Lung carcinoma are a similar example of dormancy, but with a twist....the primary in this case makes the lung mets sleep until it is removed. Then they expode. This suggests that the primary (secreting endostatin in the mouse) lulls the escaped (migrating) met cells non-proliferative, as they remain as micro-mets until the primary is removed from the mouse's back, or unless TGFB is injected near the lungs, or unless surgical disturbance wakes them up. I thought this was a very good question to consider. Thank you,.

Andrew Maniotis, PhD

This is surely a good question.Different tumor types have different phenotypes, the best way to detect whether proliferation and metastasis of one cancer cell line are indeed coupled is to perform wound-healing assay with inhibiting its proliteration.By comparing the wound-healing rate and the inhibiting degree of proliferation, we can judge whether proliferation and metastasis are coupled on earth in some cancer cell model.