{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ray U"],"funding":["American Cancer Society","NCI NIH HHS","DoD OCRP Ovarian Cancer Academy Award","NIH","ATCC"],"pagination":["1038-1054"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8930558"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["82(6)"],"pubmed_abstract":["Dissemination of ovarian cancer cells can lead to inoperable metastatic lesions in the bowel and omentum that cause patient death. Here we show that LRRC15, a type-I 15-leucine-rich repeat-containing membrane protein, highly overexpressed in ovarian cancer bowel metastases compared with matched primary tumors and acts as a potent promoter of omental metastasis. Complementary models of ovarian cancer demonstrated that LRRC15 expression leads to inhibition of anoikis-induced cell death and promotes adhesion and invasion through matrices that mimic omentum. Mechanistically, LRRC15 interacted with β1-integrin to stimulate activation of focal adhesion kinase (FAK) signaling. As a therapeutic proof of concept, targeting LRRC15 with the specific antibody-drug conjugate ABBV-085 in both early and late metastatic ovarian cancer cell line xenograft models prevented metastatic dissemination, and these results were corroborated in metastatic patient-derived ovarian cancer xenograft models. Furthermore, treatment of 3D-spheroid cultures of LRRC15-positive patient-derived ascites with ABBV-085 reduced cell viability. Overall, these data uncover a role for LRRC15 in promoting ovarian cancer metastasis and suggest a novel and promising therapy to target ovarian cancer metastases.Significance: This study identifies that LRRC15 activates β1-integrin/FAK signaling to promote ovarian cancer metastasis and shows that the LRRC15-targeted antibody-drug conjugate ABBV-085 suppresses ovarian cancer metastasis in preclinical models."],"journal":["Cancer research"],"pubmed_title":["Targeting LRRC15 Inhibits Metastatic Dissemination of Ovarian Cancer."],"pmcid":["PMC8930558"],"funding_grant_id":["OVCAR 7/5/10","P50 CA136393","TOV21G","W81XWH-15-0253","P30 CA015083","P50CA136393","RSG-21-019-01-CSM"],"pubmed_authors":["Dasari S","Thirusangu P","Xiao Y","Roy B","Shridhar V","Jung DB","Staub JK","Hou X","Sarkar Bhattacharya S","Mitra AK","Ray U","Kannan N","Roy D","Bakkum-Gamez JN","Kaufmann SH","Purcell JW","Weroha SJ","Jin L"],"additional_accession":[]},"is_claimable":false,"name":"Targeting LRRC15 Inhibits Metastatic Dissemination of Ovarian Cancer.","description":"Dissemination of ovarian cancer cells can lead to inoperable metastatic lesions in the bowel and omentum that cause patient death. Here we show that LRRC15, a type-I 15-leucine-rich repeat-containing membrane protein, highly overexpressed in ovarian cancer bowel metastases compared with matched primary tumors and acts as a potent promoter of omental metastasis. Complementary models of ovarian cancer demonstrated that LRRC15 expression leads to inhibition of anoikis-induced cell death and promotes adhesion and invasion through matrices that mimic omentum. Mechanistically, LRRC15 interacted with β1-integrin to stimulate activation of focal adhesion kinase (FAK) signaling. As a therapeutic proof of concept, targeting LRRC15 with the specific antibody-drug conjugate ABBV-085 in both early and late metastatic ovarian cancer cell line xenograft models prevented metastatic dissemination, and these results were corroborated in metastatic patient-derived ovarian cancer xenograft models. Furthermore, treatment of 3D-spheroid cultures of LRRC15-positive patient-derived ascites with ABBV-085 reduced cell viability. Overall, these data uncover a role for LRRC15 in promoting ovarian cancer metastasis and suggest a novel and promising therapy to target ovarian cancer metastases.Significance: This study identifies that LRRC15 activates β1-integrin/FAK signaling to promote ovarian cancer metastasis and shows that the LRRC15-targeted antibody-drug conjugate ABBV-085 suppresses ovarian cancer metastasis in preclinical models.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-09T13:28:03.627Z","creation":"2025-05-29T16:10:46.242Z"},"accession":"S-EPMC8930558","cross_references":{"pubmed":["34654724"],"doi":["10.1158/0008-5472.CAN-21-0622"]}}