Understanding micrometastatic disease and Anoikis resistance in ewing family of tumors and osteosarcoma

Abstract

Detection of micrometastatic tumor cells in the bone marrow or peripheral blood of patients with Ewing family of tumors (EFTs) and osteosarcoma has been shown to correlate with poor outcome. Although one of the aims of chemotherapy is eradication of micrometastatic disease, these cells vary phenotypically from primary tumor cells and appear to be more resistant to chemotherapy. As a barrier to metastasis, cells normally undergo a form of cell death termed anoikis after they lose contact with the extracellular matrix or neighboring cells. Tumor cells that acquire malignant potential have developed mechanisms to resist anoikis and thereby survive after detachment from their primary site and while traveling through the circulation. Investigating mechanisms of resistance to anoikis, therefore, provides a valuable model to investigate regulation of micrometastatic disease. This review focuses on the current understanding of the mechanisms involved in mediating cell survival and resistance to anoikis in EFTs and osteosarcoma and discusses future studies that may help to identify novel therapeutics targeted at micrometastatic disease.

Figure 1.

Metastasis involves several steps in which tumor cells disseminate from the primary site to secondary metastatic sites. Anoikis resistance allows tumor cells to survive in the absence of adhesion to the extracellular matrix, in the circulation or lymphatic system and travel to secondary sites in distant organs. Adapted from Simpson CD, Anyiwe K, Schimmer AD. Anoikis resistance and tumor metastasis. Cancer Lett 2008;272:177–185; with permission from Elsevier.