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CD109 is a novel cancer stem-like cell marker for the diagnosis of ovarian
cancer

Jun Se Kim*, Dae Kyoung Kim, Seo Yul Lee, Min Joo Shin, Ho Jun Kim, Seong Min Choi and Jae Ho Kim
Department of Physiology, School of Medicine, Pusan National University, Yangsan- si,50612

Abstract

Ovarian cancer is the deadliest gynecological
malignancy due to development of chemoresistance
and relapse. To enhance the therapeutic effect of
ovarian cancer, it is necessary to develop an effective
method for identification, isolation, and targeting of
ovarian cancer stem cells. In this study, we isolated
CSCs through sphere culture of A2780 epithelial
ovarian cancer cells and primary ovarian cancer cells
derived 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
efficiency, cell migration and ALDH activity. CD109
overexpression in adherent A2780 cells increased
cancer stem cell properties, such as spheroid-
forming efficiency, cell migration and the ALDH FIGURE 6. CD109 is involved drug resistance ability through
regulation of ABC-transporters.
activity. Furthermore, the analysis of patient-derived
ovarian cancer cells shows that there is a correlation
between 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 FIGURE 3. CD109 expression in ovarian cancer cells and
important target in the development of therapeutics ovarian cancer stem cells.
for ovarian cancer patients.

Results

FIGURE 4. CD109 positively regulates ALDH activity and
sphere formation in ovarian cancer cells.

FIGURE 1. Over-confluent cultures of A2780 ovarian cancer
stem cells.
FIGURE 7. The expression of CD109 on ovarian tumor
Description Gene Genbank GeneID SPH/WT WT signal SPH signal correlated with pool survival in ovarian cancer patients.
Accession value value
aldehyde dehydrogenase 1 ALDH1A2 AB015228 Hs.643455 186.884 16.610 3104.187
Conclusion
family, member A2
CD109 molecule CD109 AL110152 Hs.399891 155.848 7.341 1144.102
CD109 expression is increased in ovarian cancer stem
collagen, type XII, alpha 1 COL12A1 U73778 Hs.101302 91.964 19.521 1795.288
cells, and CD109 is considered necessary for
maintaining the cancer stem cell properties, such as
collagen, type XII, alpha 1 COL12A1 AA788946 Hs.101302 31.493 91.964 2896.309
self-renewal and the drug resistance in vitro.
Furthermore, the analysis of patient-derived ovarian
forkhead box P1 FOXP1 AW080845 Hs.431498 24.437 14.152 345.849
cancer cells shows that there is a correlation
between CD109 expression and patient survival.
prominin 1 PROM1 NM_006017 Hs.614734 14.084 6.9016 97.207 FIGURE 5. CD109 promotes cell migration and invasion in Therefore, CD109 may be an important target in the
ovarian cancer cell.
development of therapeutics for ovarian cancer
patients.
FIGURE 2. The expression of ALDH1 and CD109 in spheroid-
derived cells by Micro-array