Addressing the role of cell adhesion in tumor cell dormancy.
The dissemination of tumor cells prior to the surgical resection of early stage tumors poses a serious risk to the disease free survival of cancer patients. This risk arises from the latent capacity of these cells to form solid metastatic lesions after a prolonged period of dormancy, exacerbated by the fact that these cells are often refractory to adjuvant chemotherapeutic protocols. Ensuring the long term survival of cancer patients therefore necessitates an understanding of the mechanisms of tumor cell dormancy and the accompanying drug resistance. Experiments designed to compare the biological behavior of metastatic versus nonmetastatic variants of tumor cells provide evidence that there exists a phenomenon of single-cell dormancy which may depend on a reciprocal dialogue between the tumor cell and the tissue microenvironment. Through a combination of 3-dimensional cell culture technique and in vivo models investigators are now beginning to elucidate the molecular mechanisms underlying this phenomenon. Here we review the results of a series of experiments describing the role of cell adhesion events in dictating tumor cell behavior, including the balance between proliferation and dormancy, and the acquisition of drug resistance.
White
Donald E
DE
Molecular Oncology Group and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.
Rayment
Jonathan H
JH
Muller
William J
WJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001485:Basement Membrane / Q000378:metabolism; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
D000970:Antineoplastic Agents; D039641:Integrin beta Chains