Targeting LRRC15 Inhibits Metastatic Dissemination of Ovarian Cancer

Upasana Ray, Deok Beom Jung, Ling Jin, Yinan Xiao, Subramanyam Dasari, Sayantani Sarkar Bhattacharya, Prabhu Thirusangu, Julie K. Staub, Debarshi Roy, Bhaskar Roy, S. John Weroha, Xiaonan Hou, James W. Purcell, Jamie N. Bakkum-Gamez, Scott H. Kaufmann, Nagarajan Kannan, Anirban K. Mitra, Viji Shridhar

Research output: Contribution to journalArticlepeer-review


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 repeatcontainingmembrane 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 latemetastatic 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.

Original languageEnglish (US)
Pages (from-to)1038-1054
Number of pages17
JournalCancer research
Issue number6
StatePublished - Mar 15 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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