Tumor endothelial cells accelerate tumor metastasis

Abstract

Tumor metastasis is the main cause of cancer-related deaths. Understanding the molecular mechanisms underlying tumor metastasis is crucial to control the fatal disease. Several molecular pathways orchestrate the complex cell biological events during a metastatic cascade. It is now well known that bidirectional interaction between the tumor cells and their microenvironment, including tumor stroma, is important for tumor progression and metastasis. Tumor stromal cells, which acquire their specific characteristics in the tumor microenvironment, accelerate tumor malignancy. The formation of new blood vessels, termed as tumor angiogenesis, is a requirement for tumor progression. Tumor blood vessels supply nutrient and oxygen and also provide the route for metastasis. Tumor endothelial cells, which line tumor blood vessels, also exhibit several altered phenotypes compared with those of their normal counterparts. Recent studies have emphasized on "angiocrine factors" that are released from tumor endothelial cells and promote tumor progression. During intravasation, tumor cells physically contact tumor endothelial cells and interact with them via the juxtacrine and paracrine signaling. Recently, we observed that in highly metastatic tumors, tumor endothelial cells interact with the tumor cells via the secretion of a small leucine-rich repeat proteoglycan known as biglycan. Biglycan from tumor endothelial cells stimulates the tumor cells to metastasize. In this review, we have highlighted the role of tumor stromal cells, particularly endothelial cells, in the initial steps of tumor metastasis.

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