Cell motility plays an important role in many biological processes, like cancer metastasis. Of particular importance in these processes is chemotaxis: directed motility towards increasing concentrations of soluble factors. Cancer metastasis is a complex process that involves a number of events, with multiple signals from tumor and stromal cells, the extracellular matrix, and soluble growth factors inﬂuencing the behavior of cancer cells.
In order to understand and subsequently treat metastasis, we need to understand the mechanism of cancer cell chemotaxis in response to EGF and other chemoattractants. One of the most important, and best understood, growth factor systems in this regard is the epidermal growth factor/epidermal growth factor response (EGF/EGFR) system, long implicated in cancer development. Traditionally associated with tumor cell proliferation and growth, EGFR expression has been found to correlate with the metastatic potential of various cancers. On the cellular level, EGF was shown to induce chemotaxis of metastatic breast cancer cells, both in vivo and in vitro. This is particularly relevant to metastasis, since platelets, smooth muscle cells, monocytes, and macrophages have been shown to produce EGF along with platelet-derived growth factor (PDGF) and related growth factors. Gradients resulting from the release of these factors may provide chemotactic cues that direct metastatic cell motility towards blood vessels, where they can enter the blood stream and travel to other sites in the body. Antibodies act at the receptor level and block all the downstream signaling associated with the receptor, thus inhibiting the entire chemotactic response. Inhibitors that act further downstream may only block certain aspects of the chemotactic response, leaving the rest of the process intact.
The mechanism of action of the inhibitor could be used as a measure of its effectiveness in metastasis therapy. One can envision a situation where a chemoattractant is speciﬁcally associated with cancer cell metastasis, and does not inﬂuence other cells. In such a case, inhibitors that completely block chemotaxis may be more effective, and may result in the best therapeutic outcome. This knowledge may result in novel approaches for treatment of metastasis that target cell motility.
Saadi, W., Wang, S., Lin F., Li, N. “A parallel-gradient microfluidic chamber for quantitative analysis of breast cancer cell chemotaxis”/ Biomedical Microdevices. Volume 8, Number 2, 109-118, DOI: 10.1007/s10544-006-7706-6