Endo180 modulation by bisphosphonates and diagnostic accuracy in metastatic breast cancer

Abstract

Background:Endo180 (CD280; MRC2; uPARAP)-dependent collagen remodelling is dysregulated in primary tumours and bone metastasis. Here, we confirm the release and diagnostic accuracy of soluble Endo180 for diagnosing metastasis in breast cancer (BCa).Methods:Endo180 was quantified in BCa cell conditioned medium and plasma from BCa patients stratified according to disease status and bisphosphonate treatment (n=88). All P-values are from two-sided tests.Results:Endo180 is released by ectodomain shedding from the surface of MCF-7 and MDA-MB-231 BCa cell lines. Plasma Endo180 was significantly higher in recurrent/metastatic (1.71±0.87; n=59) vs early/localised (0.92±0.37; n=29) BCa (P<0.0001). True/false-positive rates for metastasis classification were: 85%/50% for the reference standard, CA 15-3 antigen (28 U ml−1); ⩽97%/⩾36% for Endo180; and ⩽97%/⩾32% for CA 15-3 antigen+Endo180. Bisphosphonate treatment was associated with reduced Endo180 levels in BCa patients with bone metastasis (P=0.011; n=42). True/false-positive rates in bisphosphonate-naive patients (n=57) were: 68%/45% for CA 15-3 antigen; ⩽95%/⩾20% for Endo180; and ⩽92%/⩾21% for CA 15-3 antigen+Endo180.Conclusion:Endo180 is a potential marker modulated by bisphosphonates in metastatic BCa.

Extracellular matrix endocytosis in controlling matrix turnover and beyond: emerging roles in cancer

“…Moreover, overexpression of Endo180, but not an endocytosis-deficient mutant, in MCF7 breast cancer cells promotes tumour growth in mouse xenograft experiments, highlighting the contribution of ECM internalisation to cancer formation in vivo [42] (figure 3B). Consistently, Endo180 levels are increased in metastatic breast cancer patients compared to patients bearing localised (non-invasive) breast cancer [43], suggesting that ECM internalisation might be an important player in the metastatic cascade.…”

A soluble form of the macrophage-related mannose receptor (MR/CD206) is present in human serum and elevated in critical illness

“…One of these proteins, Endo180, was recently found to be shed from breast cancer cells in a soluble form, sEndo180. Furthermore, Endo180 was elevated in patients with metastatic breast cancer and reduced in response to bisphosphonate treatment [26]. These findings support the potential of the MR family as serum biomarkers.…”

Survival Outcome and EMT Suppression Mediated by a Lectin Domain Interaction of Endo180 and CD147

“…In combination with the continued validation of soluble Endo180 in serum as a highly sensitive and specific biomarker for metastatic disease (39), the findings of this study suggest that strategies for antimetastatic therapy should (a) promote stabilization of the suppressive complex between CTLD4 in Endo180 and CD147 at the plasma membrane, in the case of indolent diseases like BPH, and (b) exclusively target endosomal Endo180, in the case of aggressive tumors. We predict that the aligned introduction of Endo180 as a prognostic marker and therapeutic target will have a significant impact on the prognosis Schematic showing how Endo180-CTLD4 and CD147 complex stabilizes normal epithelial apical-to-basal cell polarity.…”