Objectives 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.
Methods Immunohistochemical analysis of clinical colorectal cancer samples and a colorectal carcinoma model were used.
Key findings 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-1 alpha (HIF-1 alpha) using siRNA reduced the release of inflammatory factors and the degree of MC degranulation.
Conclusions Mast cells promote the development of colorectal cancer, and MC-derived HIF-1 alpha plays an important role in regulating MC function. Our study reveals a novel role of MC-derived HIF-1 alpha in the colorectal carcinoma microenvironment.
[1]Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Dept Gen Surg, 301 Yanchang Rd, Shanghai 200072, Peoples R China.
[2]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, 268,130 Meilong Rd, Shanghai 200237, Peoples R China.
[3]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, 268,130 Meilong Rd, Shanghai 200237, Peoples R China.
[4]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Cent Lab, 164 Lanxi Rd, Shanghai 200062, Peoples R China.
[5]Shanghai Univ Tradit Chinese Med, Intervent Canc Inst Chinese Integrat Med, 164 Lanxi Rd, Shanghai 200062, Peoples R China.
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