L1CAM is required for early dissemination of fallopian tube carcinoma precursors to the ovary

• Published in: Communications biology 2022-12, Vol.5 (1), p.1362-17, Article 1362
• Main Authors: Doberstein, Kai, Spivak, Rebecca, Reavis, Hunter D., Hooda, Jagmohan, Feng, Yi, Kroeger, Paul T., Stuckelberger, Sarah, Mills, Gordon B., Devins, Kyle M., Schwartz, Lauren E., Iwanicki, Marcin P., Fogel, Mina, Altevogt, Peter, Drapkin, Ronny
• Format: Article
• Language: English
• Subjects: 13/106; 13/51; 14/1; 14/19; 38/39; 38/89; 42/41; 631/67/1517/1709; 692/4028/67/1517/1709; AKT protein; Biology; Biomedical and Life Sciences; Cell adhesion molecules; Cell culture; Cell survival; Cystadenocarcinoma, Serous - metabolism; Developmental stages; Extracellular matrix; Fallopian tube; Fallopian Tube Neoplasms - metabolism; Fallopian Tube Neoplasms - pathology; Fallopian tubes; Fallopian Tubes - metabolism; Fallopian Tubes - pathology; Female; Fibronectin; Humans; Integrins; Lesions; Life Sciences; Metabolic pathways; Neural Cell Adhesion Molecule L1 - metabolism; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - pathology; Tumors
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-022-04314-8

Most ovarian high-grade serous carcinomas (HGSC) arise from Serous Tubal Intraepithelial Carcinoma (STIC) lesions in the distal end of the fallopian tube (FT). Formation of STIC lesions from FT secretory cells leads to seeding of the ovarian surface, with rapid tumor dissemination to other abdominal structures thereafter. It remains unclear how nascent malignant cells leave the FT to colonize the ovary. This report provides evidence that the L1 cell adhesion molecule (L1CAM) contributes to the ability of transformed FT secretory cells (FTSEC) to detach from the tube, survive under anchorage-independent conditions, and seed the ovarian surface. L1CAM was highly expressed on the apical cells of STIC lesions and contributed to ovarian colonization by upregulating integrins and fibronectin in malignant cells and activating the AKT and ERK pathways. These changes increased cell survival under ultra-low attachment conditions that mimic transit from the FT to the ovary. To study dissemination to the ovary, we developed a tumor-ovary co-culture model. We showed that L1CAM expression was important for FT cells to invade the ovary as a cohesive group. Our results indicate that in the early stages of HGSC development, transformed FTSECs disseminate from the FT to the ovary in a L1CAM-dependent manner. L1CAM is implicated as an important factor that enables early fallopian tube cancer precursors to seed the ovary by promoting cell survival through extracellular matrix signaling, thereby facilitating ovarian cancer growth.