Interaction with the Extracellular Matrix Maintains Tumor Dormancy

For example, approximately 30% of breast cancer patients diagnosed with early-stage disease have been found to have breast cancer cells in their bone marrow. However, these cells seem to exist primarily as micrometastases that do not manifest themselves clinically in any way. Although many of these disseminated tumor cells may not survive for extended periods, a subset of them may represent latent but viable cells that could begin to proliferate years later.

Studies to identify the mechanisms that regulate the switch from dormancy to proliferative metastatic growth have suffered from the lack of experimental models of tumor cell dormancy.

In the current study, investigators at the [U.S.] National Cancer Institute (Bethesda, MD, USA) employed a three-dimensional cell culture system that allowed them to observe the interaction between tumor cells and surrounding extracellular matrix (ECM) under conditions closely resembling those inside the body.

They reported in the August 1, 2008, online edition of the journal Cancer Research that the tumor microenvironment was the critical regulator of cancer progression. The ECM significantly affected tumor biology and progression by providing factors for cell growth and survival and for stimulating the growth of new blood vessels to feed the tumor. Furthermore, cell adhesion to the ECM triggered signaling pathways that controlled various phases of cell growth.

Senior author Dr. Jeffrey E. Green, a senior investigator at the National Cancer Institute's laboratory of cell biology and genetics, said, "Recent evidence suggests that, in many cases, tumor cells have already seeded metastatic sites even when the primary tumor is diagnosed at an early stage. We hope that, with additional studies, we can begin to discover new ways to therapeutically keep the dormant-to-active switch in the "off” position, thus limiting the chance that micrometastases become active in later life.”

Related Links:
National Cancer Institute