Page 97 - D. Cancer biology

CD109 is a new surface protein marker for ovarian cancer stem cells

Ye Eun Kim, Dae Kyoung Kim, Min Joo Shin, Seo Yul Lee and Jae Ho Kim
Department of Physiology, School of Medicine, Pusan National University, Yangsan- si,50612, Korea

BACKGROUND

Ovarian cancer is one of the deadliest
gynecologic malignancy with the late
detection of cancer development. For the
improvement in the therapy for ovarian
cancer, a development of efficient method
for identification, isolation, and targeting of
ovarian cancer stem cells are necessary. In
this study, we isolated CSCs through
sphere culture of A2780 epithelial ovarian
cancer cells and primary ovarian cancer
cells from patients. We identified the
expression of CD109 in A2780 ovarian
cancer cells and observed that the intensity
and the frequency CD109 expression
significantly increased in the sphere culture
of A2780 ovarian cancer cells (A2780-SP).
CD109 knockdown in spheroid cells
reduced the cell migration and spheroid-
forming efficiency and ALDH activity. FIGURE 6. CD109 is involved drug resistance
CD109 overexpression in adherent A2780 ability through regulation of ABC-transporters.
cells increased cancer stem cell properties,
including cell migration, spheroid-forming
efficiency and the ALDH activity.
Furthermore, the analysis of ovarian cancer
patient sample shows the more malignant FIGURE 3. CD109 expression in ovarian
cancer cells and ovarian cancer stem cells.
the cancer correlation with CD109
expression and patient survival. Together,
our results provide novel insights regarding
the critical role of CD109 in the regulation of
the cancer stem cell characteristics of
ovarian cancer cells, thus suggesting that
CD109 may be an important target in the
development of therapeutics for ovarian
cancer patients.

RESULTS

FIGURE 4. CD109 positively regulates
ALDH activity and sphere formation in
ovarian cancer cells. FIGURE 7. The expression of CD109 on ovarian
tumor correlated with pool survival in ovarian cancer
patients.
CONCLUSION

Ovarian cancer stem cell show the high
expression of CD109, and CD109
FIGURE 1. Over-confluent cultures of A2780 ovarian expression is necessary for maintaining
cancer stem cells.
the cancer stem cell self-renewal and the
drug resistance in vitro. Furthermore, the
analysis of ovarian cancer patient sample
shows the more malignant the cancer
correlation with CD109 expression and
patient survival. Together, our results
provide novel insights regarding the
critical role of CD109 in the regulation of
the cancer stem cell characteristics of
ovarian cancer cells. CD109 may be an
important target in the development of
FIGURE 5. CD109 promotes cell migration therapeutics for ovarian cancer patients.
FIGURE 2. The expression of ALDH and CD109 in and invasion in ovarian cancer cell.
spheroid-derived cells by Micro-array