02515nas a2200421   4500000000100000000000100001008004100002260001500043653001200058653003100070653000900101653001900110653002900129653002000158653001900178653001100197653001100208653000900219653001400228653002200242653001400264653001300278653001400291100001700305700001600322700002800338700001800366700002600384700002200410700002000432700002100452700002300473245010500496300001100601490000800612520145900620022001402079       2022                            d  c2022-09-0110aAnimals10aCystadenocarcinoma, Serous10aEGFR10aErbB Receptors10aFallopian Tube Neoplasms10aFallopian Tubes10aFallopian tube10aFemale10aHumans10aMice10aMigration10aOvarian Neoplasms10aOvulation10aVersican10aVersicans1 aAngela Russo1 aZizhao Yang1 aGeorgette Moyle Heyrman1 aBrian P. Cain1 aAlfredo Lopez Carrero1 aBrett C. Isenberg1 aMatthew J. Dean1 aJonathan Coppeta1 aJoanna E. Burdette00aVersican secreted by the ovary links ovulation and migration in fallopian tube derived serous cancer  a2157790 v5433 aHigh grade serous ovarian cancers (HGSOC) predominantly arise in the fallopian tube epithelium (FTE) and colonize the ovary first, before further metastasis to the peritoneum. Ovarian cancer risk is directly related to the number of ovulations, suggesting that the ovary may secrete specific factors that act as chemoattractants for fallopian tube derived tumor cells during ovulation. We found that 3D ovarian organ culture produced a secreted factor that enhanced the migration of FTE non-tumorigenic cells as well as cells harboring specific pathway modifications commonly found in high grade serous cancers. Through size fractionation and a small molecule inhibitors screen, the secreted protein was determined to be 50-100kDa in size and acted through the Epidermal Growth Factor Receptor (EGFR). To correlate the candidates with ovulation, the PREDICT organ-on-chip system was optimized to support ovulation in a perfused microfluidic platform. Versican was found in the correct molecular weight range, contained EGF-like domains, and correlated with ovulation in the PREDICT system. Exogenous versican increased migration, invasion, and enhanced adhesion of both murine and human FTE cells to the ovary in an EGFR-dependent manner. The identification of a protein secreted during ovulation that impacts the ability of FTE cells to colonize the ovary provides new insights into the development of strategies for limiting primary ovarian metastasis.  a1872-7980