Open AccessBiological heterogeneity of putative bladder cancer stem‐like cell populations from human bladder transitional cell carcinoma samples
Author(s) -
Bentivegna Angela,
Conconi Donatella,
Panzeri Elena,
Sala Elena,
Bovo Giorgio,
Viganò Paolo,
Brunelli Silvia,
Bossi Mario,
Tredici Giovanni,
Strada Guido,
Dalprà Leda
Publication year - 2010
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2009.01414.x
Subject(s) - biology , stem cell , transitional cell carcinoma , bladder cancer , transitional cell , cell culture , cancer stem cell , stem cell marker , karyotype , pathology , cell , cancer research , cancer , microbiology and biotechnology , genetics , chromosome , medicine , gene
Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of cells, the cancer stem‐like cells (CSCs) or tumor initiating cells. We report on the isolation and biological characterization of putative bladder CSC populations from primary TCCs. Isolated cells were induced to proliferate in stem cell culture conditions (serum‐free medium containing mitogenic growth factors). The proliferating cells formed spheroids (urospheres) and their abilities for extensive proliferation and self‐renewal were assayed. Their positivity for several stem cell markers (CD133, Oct‐3/4, nestin, and cytokeratins) was also assessed by immunofluorescence tests and they could have the potential to differentiate in the presence of serum. In stem cell culture conditions they gradually showed loss of proliferation, adherence to the substrate, and morphological changes, which might reflect their progressive acquisition of differentiative capacity and loss of self‐renewal ability. To evaluate if effective cell selection occurred after isolation, conventional cytogenetic studies on fresh chromosome spreads immediately after isolation and after culture were carried out. In addition, a molecular cytogenetic study by UroVysion assay was carried out on paraffin‐embedded tissue sections and on fresh and after culture nuclei preparations. The data collected indicated important karyotype changes and a positive selection for hypo‐ or near‐diploid cells, losing the complexity present in fresh tumors. ( Cancer Sci 2009)