Cancer Paper 4/23/14 Hosein Kouros-Mehr
Cancer-Secreted miR-105 Destroys Vascular Endothelial Barriers to Promote Metastasis
Zhou et. a., Cancer Cell, Volume 25, Issue 4, p501–515, 14 April 2014
A recent paper suggests a new mechanism for metastasis of cancer cells to distant organs. Metastasis is a complex process consisting of a series of steps that a cancer cell must achieve to establish de novo cancers in distant organs. One of the rate-limiting steps in metastasis is the extravasation and growth of disseminated cells that have reached the vasculature of the distant organ. Here the disseminated cells face several barriers: (1) extravasation across the microvasculature of the distant site, including migration through the endothelial cell layer and basement membrane; (2) survival in the new microenvironment of the distant organ; (3) evasion of the immune response in the distant organ.
Zhou et al. suggest that tumor cells can secrete microRNAs to assist them in the metastatic process. Namely, they suggest that tumors cells can secrete miR-105 into their microenvironment, which targets the ZO-1 tight junction protein gene in endothelials at sites of tumor dissemination. This allows downregulation of tight junction proteins in endothelial cells, which then allows cancer cells to extravasate into distant organs. Interestingly, circulating miR-105 was found to predict metastasis in early-stage breast cancer patients.
New targets/drugs for oncology have traditionally focused on signaling pathways required for primary tumor cell proliferation and growth. While many new cancer drugs have come to market over the last few decades, the overall survival rate of cancer has not decreased as greatly as expected. Metastasis is the primary cause of mortality and morbidity in cancer and new drugs that block metastasis may help increase cancer survival rates.
Hosein Kouros-Mehr
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