Ovarian cancer immuno-reactive antigen domain containing 1 (OCIAD1), a key player in ovarian cancer cell adhesion.
OBJECTIVE
To identify proteins unique to metastatic ovarian cancer and test their potential involvement in cell adhesion.


METHODS
We purified plasma membrane from paired metastatic and primary tumor tissues from patients with stage IIIC ovarian cancer. Membrane proteins unique to metastases were identified by liquid chromatographic mass spectrometry (LC-MS). The role of one of the identified proteins, ovarian cancer immuno-reactive antigen domain containing 1 (OCIAD1) in cell adhesion was determined in the presence of LPA using both over-expression and down regulation approaches.


RESULTS
We identified a differentially expressed 29 kDa protein as OCIAD1 over-expressed in metastatic tissues, when compared to primary tumor tissues. OCIAD1 over-expression in HEY ovarian cancer cells increased LPA-induced, but not basal level cell adhesion to extracellular matrix proteins collagen I and laminin 10/11. This enhancement was not blocked by LY294002 and GF109203X, suggesting that OCIAD1 does not use PKC and PI3K signaling pathways to exert its effect on adhesion. In addition, LPA induced cell adhesion to collagen I was unaffected by paclitaxel (5 microM) in OCIAD1 overexpressing cells.


CONCLUSIONS
This is the first report that OCIAD1 is over-expressed in metastatic ovarian cancer tissues. The effect of OCIAD1 on cell adhesion may be related to its function in ovarian cancer. Failure of paclitaxel to affect ovarian cancer cell adhesion in presence of OCIAD1 raises the possibility of OCIAD1's role in tumor metastasis. Ongoing studies using a mouse orthotopic LPA-dependent ovarian cancer metastasis model are focused on strategies to inhibit the potential role of OCIAD1 in tumor metastasis.
Sengupta
Saubhik
S
Department of Obstetrics and Gynecology, Section of Gynecologic Oncology, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. sengups2@ccf.org
Michener
Chad M
CM
Escobar
Pedro
P
Belinson
Jerome
J
Ganapathi
Ram
R
D000230:Adenocarcinoma / Q000378:metabolism / Q000503:physiopathology* / Q000556:secondary; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017239:Paclitaxel / Q000494:pharmacology; D020033:Protein Isoforms / Q000494:pharmacology; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic; D024042:Collagen Type I; D007797:Laminin; D008246:Lysophospholipids; D009363:Neoplasm Proteins; D020033:Protein Isoforms; C529235:ovarian cancer immuno-reactive antigen domain containing 1, human; D017239:Paclitaxel; C032881:lysophosphatidic acid