Effects of pericytes and colon cancer stem cells in the tumor microenvironment

Abstract

Colorectal cancer (CRC) is one type of tumor with the highest frequency and mortality worldwide. Although current treatments increase patient survival, it is important to detect CRC in early stages; however, most CRC, despite responding favorably to treatment, develop resistance and present recurrence, a situation that will inevitably lead to death. In recent years, it has been shown that the main reason for drug resistance is the presence of colon cancer stem cells (CSC). Pericytes are also capable of tumor homing and are important cellular components of the tumor microenvironment (TME), contributing to the formation of vessels and promoting metastasis; however, they have not been considered very important as a therapeutic target in cancer. In this review, we highlight the contribution of pericytes and cancer stem cells to some classical hallmarks of cancer, namely, tumor angiogenesis, growth, metastasis, and evasion of immune destruction, and discuss therapies targeting pericytes and cancer stem cells in CRC.

Cancer Stem Cells and Its Role in Angiogenesis and Vasculogenic Mimicry in Gastrointestinal Cancers

“…Interestingly, neovascularization is an important process to support tumor growth and metastasis; usually, tumors reach a size of ∼2 mm in diameter when not fed by neovascularization (53). In this regard, CSCs are able to modify tumoral microenvironment by expressing angiogenic factors in order to enhance tumor neovascularization, contributing finally in their maintenance and proliferation (5).…”

“…CRCSCs are able to initiate vascularization via pericytes by growth promotion (5,60). Thus, lack of pericytes recruitment impacts negatively in tumor size owing to poor vascular structure (61).…”

“…This is also correlated to worst prognosis, due to leaky vessels that produces elevated local pressure, enhancing progression and metastasis. Nevertheless, higher vascular density has been associated with recurrence, metastasis and patient mortality (5,62).…”

“…Self-renewal of CSCs and initiation of tumor is accompanied by the promotion of angiogenesis, through the secretion of proangiogenic factors such as Vascular Endothelial Growth Factor (VEGF) (5). However, angiogenesis is not the unique source of nutrients and oxygen for tumors (6), given that CSCs are able to transdifferentiate into endothelial-like cells enhancing neovascularization (7).…”

Pericytes Relationship with Cancer Stem Cells in the Colon

“…The tumor microenvironment (TME) is defined as every piece of the components that surround and feed or maintain the tumor. It includes normal non-cancerous cells, molecules, and blood vessels near tumor cells [33]. Pericytes, within this framework, are a cell population that functions as stem cells, as mentioned previously, forming several cell types in a variety of pathophysiologic conditions, with self-renewal capacity and the potential to differentiate into multiple cell types such as adipocytes, chondrocytes, osteocytes, phagocytes, granulocytes, and myocytes, in culture [15].…”