The Cellular Microenvironment and Metastases
Summary of Key Points
• Metastases are responsible for more than 90% of all cancer-related deaths.
• Gene mutations, the tumor microenvironment, and host cells drive the metastatic spread of tumor cells.
• Metastasis can be subdivided into four steps: invasion, intravasation, survival in circulation, and extravasation.
• Colonization of metastatic tumor cells requires the ability to proliferate in a foreign tissue and stimulate angiogenesis.
• The formation of a premetastatic niche is essential for the growth of extravasating metastatic tumor cells.
• Organ specificity of tumor metastases is determined both by blood flow and tissue-specific factors.
• Primary tumors possess stem cells that can recapitulate the tumor from a single cell, and a subset of these cancer stem cells may inherently possess altered gene expression changes with increased metastatic potential.
• Antimetastatic therapy will likely require the targeted inhibition of many pathways that control proliferation, invasion, and angiogenesis.
1. What cell type(s) contribute to metastatic tumor progression?
2. Can tumor metastases reseed the primary tumor?
3. The hypoxic regulation of which of these molecules mediates the directional migration of tumor cells?
4. Can cancer stem cells metastasize without the support of the microenvironment?
1. Answer: D. Multiple cellular components of the tumor microenvironment contribute to metastasis, including cancer stem cells, endothelial cells, and macrophages.
2. Answer: A. Kim and colleagues recently reported that circulating tumor cells reseed the primary tumor. Furthermore, these cells represent an aggressive cell type within the primary tumor.
3. Answer: D. CXCR4/SDF1 are hypoxia-induced proteins that mediate the directional migration of tumor cells.
4. Answer: B. Recent studies have shown that components of the extracellular matrix, including periostin and tenascin C, at the distant site are required for successful metastasis of cancer stem cells.
