Collagen XVII (COL17), a cell-matrix adhesion protein, has been found to be suppressed in breast cancer. Our previous data demonstrated a preventive role of COL17 in breast cancer invasiveness. The present study used the stable COL17-overexpressing MCF7 and MDA-MB-231 cells to reveal an anti-proliferative effect of COL17 on breast cancer cell through mTOR deactivation. Cell proliferation was negatively correlated with the expression level of COL17 in a concentration-dependent manner in both conventional and three-dimensional (3D) culture systems. The correlation was confirmed by decreased expression of the proliferative marker Ki67 in COL17-expressing cells. In addition, overexpression of COL17 reduced the clonogenicity and growth of the cells. We demonstrated that COL17 affects the AKT/mTOR signaling pathway by deactivation of AKT, mTOR and downstream effectors, particularly 4EBP1. Moreover, mice xenografted with high COL17-expressing cells exhibited delayed tumor progression and prolonged survival time. The high expression of COL17A1 gene encoding COL17 is associated with low-proliferation tumors, extended tumor-free period, and overall survival of breast cancer patients. In conclusion, our results revealed the novel function of COL17 using in vitro and in vivo models and elucidated the related pathway in breast cancer cell growth and proliferation.

ObjectiveThe study aimed to investigate the potentiality of chemokines, including MCP-1, CCL15, CCL20, and CXCL14, as biomarkers for differential diagnosis between benign tumors and ovarian cancer (OC).MethodsA cross-sectional study was conducted in women aged >18 years who had adnexal masses treated with elective surgery at the HRH Maha Chakri Sirindhorn Medical Center, Srinakharinwirot University, between 2020 and 2021. The preoperative MCP-1, CCL15, CCL20, and CXCL14 serum levels were measured using a sandwich enzyme-linked immunosorbent assay. Preoperative diagnosis was defined according to the risk of malignancy index. The histological diagnosis and cancer subtype were confirmed using pathological specimens.ResultsNinety-eight participants were preoperatively diagnosed with malignant tumors. The pathological diagnosis confirmed OC in 33 patients and disclosed 27 misdiagnosed cases, of which endometriotic cyst was the most common (44.44%). CCL20 and CA125 serum levels were significantly higher in the patients with cancer than in those with benign. In addition, CCL20 level could differentiate between benign and early-stage malignancy. Furthermore, only CCL20 levels could distinguish endometriotic cysts from OC, whereas CA125 levels could not. Concordant with the serum protein level, the increased mRNA level of CCL20 was observed in ovarian cancers comparing with that in benign tissues. We found that CCL20 levels could differentiate between benign tumors and OC with 60.61% sensitivity and 75.44% specificity at the optimal cutoff value of 38.79 pg/ml. Finally, the logistic regression model integrating CCL20, CA125, and menopause status promoted diagnostic accuracy by increasing the specificity to 91.23%.ConclusionsOur study revealed the potential usefulness of CCL20 level as a biomarker for diagnosing early-stage OC with endometriosis differentiation. We recommend further studies to confirm the accuracy of CCL20 levels with the current diagnosis in a large patient sample.