The critical role of mast cell-derived hypoxia-inducible factor-1α in regulating mast cell function

During colorectal tumour progression, the tumour microenvironment becomes hypoxic, and infiltration of a large number of inflammatory cells occurs. The mast cells (MCs) are a type of immune cells plays an important role in tumour angiogenesis. However, it is unclear whether the role of MC in colorectal cancer is to promote or to inhibit tumour growth.

Immunohistochemical analysis of clinical colorectal cancer samples and a colorectal carcinoma model were used.

We found the carcinomas and the adjacent tissues were infiltrated with large numbers of mast cells, and the MC infiltration quantity increased with the Dukes' stage. After tumour inoculation, the survival time of MC-deficient mice was remarkably longer than wild-type C57BL/6 mice, and the tumour growth rate of MC-deficient mice was slower than wild type. In addition, the survival time and tumour growth rate can be recovered in MC reconstruction mice. Furthermore, inhibition of the expression of hypoxia-inducible factor-1α (HIF-1α) using siRNA reduced the release of inflammatory factors and the degree of MC degranulation.

Mast cells promote the development of colorectal cancer, and MC-derived HIF-1α plays an important role in regulating MC function. Our study reveals a novel role of MC-derived HIF-1α in the colorectal carcinoma microenvironment.