Chitinase 3 like 1 (CHI3L1) promotes vasculogenic mimicry formation in cervical cancer

Abstract

Vasculogenic mimicry (VM) is an alternative microvascular system which tumour cells orchestrate, independent of endothelial cell-mediated angiogenesis. VM develops tumour vascular networks that correlate with tumour growth, metastasis, and short survival time of patients with a number of cancers. However, little is known regarding VM in the vascularisation of cervical cancer. Chitinase 3 like 1 (CHI3L1) has been previously reported to display the ability to induce angiogenesis in cervical cancer. Here, we explored a pathological role of CHI3L1 in tumour cell-mediated vascularisation. Sixty-six samples of cervical cancer were collected to examine CHI3L1 expression and VM formation using immunohistochemistry and CD34-periodic acid-Schiff (PAS) dual staining. CHI3L1 expression was significantly correlated with formation of tumour cell-associated vascular channels in the absence of endothelial cells (p=0.031). Interestingly, tumour samples lacking VM were positively correlated with non-metastasis (p=0.035). Patients with VM positive tumours tended to have decreased overall survival (OS) compared to those with VM negative samples (43.9 versus 64.6 months, p=0.079). In addition, recombinant CHI3L1 enhanced cervical cancer cell lines to form tube-like structures, supporting the notion that CHI3L1 mediates VM in cervical cancer. Our present data reveal the crucial role of CHI3L1 in the formation of VM, which may contribute to tumour aggressiveness. Therefore, targeting CHI3L1 may be a valuable strategy for the reduction of cervical cancer vascularisation and metastasis.