CD24 expression as a marker for predicting clinical outcome and invasive activity in uterine cervical cancer.
CD24, a small heavily glycosylated mucin-like glycosyl-phosphatidylinositol-anchored cell surface protein, plays an important role in the carcinogenesis of various human malignancies. However, its function in cervical cancer remains unclear. The aim of the present study was to evaluate the expression of CD24 clinicopathologically and to analyze its functional behavior biologically in cervical cancer. A total of 117 uterine cervical cancer tumors were immunohistochemically analyzed using a CD24 monoclonal antibody on paraffin blocks. We also examined whether CD24 enhanced the invasive activity or the Akt, ERK, NF-κB and MMP activity in a uterine cervical cancer cell line (CaSki) by a western blot analysis. The patients with enhanced CD24 expression had a higher rate of advanced clinical stage (50 vs. 16.5%, p<0.01), lymph node metastasis (34.6 vs. 14.3%) and lymphovascular involvement (65.4 vs. 20.4%, p=0.01), and a poor overall and disease-free survival (5-year survival rate: 62 vs. 86%, p=0.03). CD24 overexpression in CaSki cells resulted in activation of Cell Signaling proteins, including Akt, ERK, NF-κB and MMP-9. An invasion assay showed that CD24 overexpression in CaSki cells led to increased invasion ability. The CD24 overexpression also increased mRNA expression of Slug but not Snail. Moreover, the CD24 overexpression also decreased expression of E-cadherin and increased N-cadherin protein levels. Increased expression of CD24 may be associated with tumor progression and prognosis in patients with uterine cervical cancer. CD24 expression may therefore be used not only as a prognostic marker in uterine cervical cancer, but also as a target for the development of new therapeutic approaches.
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Tomohito
T
Tanaka
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Yoshito
Y
Terai
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Yuhei
Y
Kogata
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Keisuke
K
Ashihara
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Kazuya
K
Maeda
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Satoe
S
Fujiwara
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Saha
S
Yoo
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Yoshimichi
Y
Tanaka
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Satoshi
S
Tsunetoh
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Hiroshi
H
Sasaki
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Masanori
M
Kanemura
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Akiko
A
Tanabe
Department of Obstetrics and Gynecology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
Masahide
M
Ohmichi
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D051927:CD24 Antigen / Q000378:metabolism*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D020935:MAP Kinase Signaling System; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D018307:Neoplasms, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy
D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D051057:Proto-Oncogene Proteins c-akt