Breast cancer is the leading cause of cancer-related deaths in women worldwide. Several studies have indicated that abnormal chondroitin sulfate (CS) chains accumulate in breast cancer tissues; however, the functions and dysregulation of CS synthases are largely unknown. Here, we demonstrate that chondroitin polymerising factor (CHPF) is frequently upregulated in breast cancer tissues and that its high expression is positively associated with tumor metastasis, high stages, and short survival time. CHPF modulates CS formation in breast cancer cells. Additionally, we found that CHPF promotes tumor growth and metastasis accompanied by an increase in G-CSF levels and the number of myeloid-derived suppressor cells in tumor tissue. We revealed that tumor cell-derived G-CSF is co-localised with CS on the cell surface. Interestingly, our study is the first to identify that syndecan-4 (SDC4) is modified by CHPF and that it is involved in CHPF-mediated phenotypes. Moreover, breast cancer patients with high expression of both SDC4 and CHPF had worse overall survival compared to other subsets, which implied the synergistic effects of these two genes. In summary, our results indicated that the upregulation of CHPF in breast cancer contributes to the malignant behaviour of cancer cells, thereby providing novel insights on the significance of CHPF-modified SDC4 in breast cancer pathogenesis.
Keywords: Breast cancer; CHPF; chondroitin sulfate; syndecan-4; tumor microenvironment.
AJCR Copyright © 2021.