Transcription profiling of human CD133 positive and negative colon cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Yike Wang
PROVIDER: E-MEXP-2467 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:CD133 has been widely used for identification and isolation of cancer stem cells in tumors although its role as a marker for cancer stem cell is still controversial . We isolated the CD133+ and CD133- cells from SW620 human colon cancer cell line and compared their biological characteristics, such as tumorigenicity,drug sensitivity, etc. Our study revealed that CD133+ SW620 cells were more tumorigenic and resistant to anti-cancer drugs. Correspondingly, they displayed different gene expression profile. However, it was observed that CD133- cells and CD133+ cells could mutually convert, indicating that CD133 expression was under dynamic and reversible regulations which might impose significant infulence on cells behaviors. Thus, our data challenge the role of CD133 as a marker for cancer stem cell. There are two populations with distinct expression of CD133 in SW620 human colon cancer cell line. Microarray assays were employed to investigate the differentially expressed genes between the two populations, which may possess different tumorigenetic potential and sensitivity to anti-cancer drugs. CD133+ and CD133- cells were isolated from human colon cancer SW620 cell line by magnetic cell sorting system. The clones from sorted CD133+ or CD133- populations were established. Clone cells were expanded and were further purified by using CD133 cell isolation kit before microarray assays.
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Project description:Given the very substantial heterogeneity of most human cancers, it is likely that most cancer therapeutics will be active in only a small fraction of any population of patients. As such, the development of new therapeutics, coupled with methods to match a therapy with the individual patient, will be critical to achieving significant gains in disease outcome. One such opportunity is the use of expression signatures to identify key oncogenic phenotypes that can serve not only as biomarkers but also as a means of identifying therapeutic compounds that might specifically target these phenotypes. Given the potential importance of targeting tumors exhibiting a stem-like phenotype, we have developed an expression signature that reflects common biological aspects of various stem-like characteristics. The Consensus Stemness Ranking (CSR) signature is upregulated in cancer stem cell enriched samples, at advanced tumor stages and is associated with poor prognosis in multiple cancer types. Using two independent computational approaches we utilized the CSR signature to identify clinically useful compounds that could target the CSR phenotype. In vitro assays confirmed selectivity of several predicted compounds including topoisomerase inhibitors and resveratrol towards breast cancer cell lines that exhibit a high-CSR phenotype. Importantly, the CSR signature could predict clinical response of breast cancer patients to a neoadjuvant regimen that included a CSR-specific agent. Collectively, these results suggest therapeutic opportunities to target the CSR phenotype in a relevant cohort of cancer patients. CD133+ and CD133- cells were separated from two glioma xenograft tumors. Both CD133+ and CD133- glioma cells were cultured in serum-free media for 48 hours in the presence of absence of laminin.
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