Adhesion and Beyond: CD44 in Ovarian Cancer Spheroids

The Department of Biopharmaceutical Sciences presents:

DISSERTATION DEFENSE SEMINAR

“Adhesion and Beyond: CD44 in Ovarian Cancer Spheroids”

Joelle Sacks
PhD Candidate, Biopharmaceutical Sciences
Advisor: Prof. Maria Barbolina

January 12, 2018 (Friday)
2:30 PM – 3:30 PM
Room B32 COP/ Room E223 Rockford
UIC College of Pharmacy
833 S. Wood Street, Chiago, IL

Abstract: Epithelial ovarian carcinoma (EOC) metastasis is characterized by the shedding of malignant cells from the surface of the primary tumor and their implantation onto the peritoneal surface lining the abdominal cavity in addition to more distant sites. This shedding of malignant cells from the primary site results as either single cells or free-floating multicellular aggregates, known as spheroids, in the ascites. Although single cells and spheroids may potentially seed metastases, considerable evidence now suggests that the aggregation of cells is important for anchorage-independent cell survival and growth, and spheroid formation may represent an important intermediate survival mechanism to facilitate EOC dissemination. Recent studies have uncovered human transmembrane cell adhesion molecule CD44 standard (CD44s) isoform expression correlating with high grade and advance-stage ovarian carcinoma. Moreover, it has also been suggested that CD44s may be an important mediator of ovarian cancer cell implantation in the peritoneal cavity enhancing the metastatic potential of ovarian cancer cells. Thus, we investigated the functional significance of CD44 standard by means of in vitro culture experiments with ovarian cancer spheroids. After characterizing 8 EOC cell lines, a spectrum of CD44 expression was observed and two cell lines with high CD44s (ES-2 and SKOV-3) and two cell lines low in CD44s (OVCAR-4 and OVSAHO) were chosen for further testing. Interestingly, the high CD44s-expressing cell lines formed larger spheroids that adhered significantly faster to a monolayer of primary mesothelial cells.  Silencing CD44 expression using CRISPR/Cas9 in these 2 cell lines reduced spheroid formation suggesting that differential expression of CD44s plays a role in cell-cell adhesion. When ES-2 CD44-/- cells were injected i.p into athymic nude mice, decreased ascites production and mesentery tumor burden were observed as well as increased overall survival.  However, CD44 knockout also significantly increased metastasis to the lung suggesting a suppressive role for CD44 in EOC metastasis, as well. This in vivo data implies that CD44 enhances the metastatic potential in ovarian cancer spheroids influencing peritoneal tumor growth while suppressing lung metastasis.