Cells with Characteristics of Cancer Stem/Progenitor Cells Express the CD133 Antigen in Human Endometrial Tumors

Abstract

Purpose: Cancer stem cells represent an attractive therapeutic target for tumor eradication. The present study aimed to determine whether CD133 expression may identify cells with characteristics of cancer stem/progenitor cells in human endometrial tumors. Experimental Design: We analyzed 113 tumor samples for CD133/1expression by flow cytometry, immunohistochemistry, and semiquantitative reverse transcription^PCR. CD133 + cells were isolated and used to assess phenotypic characteristics, self-renewal capacity, ability to maintain CD133 expression and form sphere-like structures in long-term cultures, sensitivity to chemotherapeutic agents, gene expression profile, and ability to initiate tumors in NOD/SCID mice. Results: Primary tumor samples exhibited a variable degree of immunoreactivity for CD133/1, ranging from1.3% to 62.6%, but stained negatively for other endothelial and stem cell^associated markers. Isolated CD133 + cells expanded up to 4.6-fold in serum-replenished cultures and coexpressed the GalNAca1-O-Ser/Thr MUC-1 glycoform, a well-characterized tumor-associated antigen. Dissociated bulk tumors formed sphere-like structures; cells grown as tumor spheres maintained CD133 expression and could be propagated for up to 12 weeks. CD133 + cells purified from endometrioid adenocarcinomas were resistant to cisplatin-induced and paclitaxelinduced cytotoxicity and expressed a peculiar gene signature consisting of high levels of matrix metalloproteases, interleukin-8, CD44, and CXCR4. When serially transplanted into NOD/SCID mice, CD133 + cells were capable of initiating tumor formation and recapitulating the phenotype of the original tumor. Conclusions: CD133 is expressed by human endometrial cancers and might represent a valuable tool to identify cells with cancer stem cell characteristics.

Inflammatory events in endometrial adenocarcinoma

“…However, the process is evidently complex, and inflammation may contribute to tumour initiation in certain cases, by working in conjunction with other mechanisms (Fortuny et al 2009). Cancer growth may therefore be initiated by genetic mutations, possibly in endometrial stem cells (Rutella et al 2009), causing uncontrolled proliferation and subsequent cellular changes. These genetic changes may be a result of increased proliferation driven by an increased oestrogen to progesterone ratio in endometrial adenocarcinoma, in agreement with the unopposed oestrogen hypothesis (Jazaeri et al 2001).…”

Immunological and Clinical Impact of Cancer Stem Cells in Vulvar Cancer: Role of CD133/CD24/ABCG2-Expressing Cells

“…In addition, we demonstrated that CD133 + CSCs isolated from endometrial cancer express the tumour-associated antigen mucin-1 (MUC1). MUC1 make these cells potentially susceptible to immune system attack and contributes to maintaining resistance to cisplatin and paclitaxel (29). Again, CD133 expression was found to be the only independent risk factor in 1,366 patients affected by ovarian cancer with central nervous system metastasis (30).…”

High-level expression of stem cell marker CD133 in clear cell renal cell carcinoma with favorable prognosis

“…The high expression of CD133 in ccRCC with favorable clinicopathological characteristics was an unexpected result, as CD133 has been applied as a putative CSC marker in numerous malignant tumors, and its high expression has been considered a poor prognostic factor. CD133 is currently applied as a cell-surface marker to isolate CSCs in malignant tumors of the colon, brain, lung, prostate, pancreas, liver, stomach and uterus (11,(25)(26)(27). A CD133…”

“…In colon cancer, high levels of CD133 expression were associated with a shorter relapse-free interval and poor overall survival (31). Furthermore, CSCs appear to be highly resistant to chemoradiation therapy (26,(32)(33)(34). In an atypical teratoid/rhabdoid tumor of the brain, high levels of CD133 + cells were positively correlated with radioresistance (35).…”