Premium
Tumor‐associated macrophage‐derived CCL5 promotes chemotherapy resistance and metastasis in prostatic cancer
Author(s) -
Ma Jian,
Shayiti Fuerhaiti,
Ma Jing,
Wei Meng,
Hua Tingting,
Zhang Rong,
Su Junyan,
Chen Peng
Publication year - 2021
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11630
Subject(s) - ccl5 , metastasis , cancer research , tumor microenvironment , stat3 , tumor associated macrophage , tumor progression , cancer , medicine , biology , immunology , immune system , signal transduction , t cell , tumor cells , il 2 receptor , microbiology and biotechnology
The crosstalk between tumor microenvironment and cancer cells is emerging as a critical determinant in tumor progression. However, the underlying mechanism of tumor microenvironment‐induced cancer development remains controversial. Here, our study provides evidence to suggest that tumor‐associated macrophage (TAM) enrichment is found in chemoresistant prostatic tumor tissues. Those TAMs are demonstrated to promote chemoresistance and distant metastasis in prostatic cancer through secretion of CCL5. Mechanistically, TAM coculture or additional CCL5 can mediate the STAT3‐dependent epithelial–mesenchymal transition process, resulting in distant metastasis in prostatic cancer. Meanwhile, activation of STAT3 induced by CCL5 can mediate upregulation of the transcription factor Nanog, leading to drug resistance. In vivo study further demonstrated that blockade of STAT3 signals significantly reverses chemoresistance and suppresses lung metastasis in colorectal tumor‐bearing mice, suggesting a novel strategy for clinical prostatic cancer treatment.