Isolation and culture of colon cancer stem cells.

Cancer stem cells (CSCs) resemble normal stem cells in several ways. Both cell types are self-renewing and when they divide, one of the daughter cells differentiates while the other retains stem cell properties, including the ability to divide in the same way again. CSCs have been demonstrated to exist in several solid tumors, including colon carcinoma; these cells are able to initiate and sustain tumor growth. There are essentially three different methods to isolate CSCs: establishment culture, the MACS (magnetic cell sorting) technology, and the FACS (fluorescence-activated cell sorting) technology.

Isolation and Culture of Colon Cancer Stem Cells

Cancer stem cells (CSCs) resemble normal stem cells in several ways. Both cell types are self-renewing and when they divide, one of the daughter cells differentiates while the other retains stem cell properties, including the ability to divide in the same way again. CSCs have been demonstrated to exist in several solid tumors, including colon carcinoma; these cells are able to initiate and sustain tumor growth. There are essentially three different methods to isolate CSCs: establishment culture, the MACS (magnetic cell sorting) technology, and the FACS (fluorescence-activated cell sorting) technology.

Bone morphogenetic protein 4 induces differentiation of colorectal cancer stem cells and increases their response to chemotherapy in mice.

BACKGROUND & AIMS: The limited clinical response observed in many patients with colorectal cancer may be related to the presence of chemoresistant colorectal can- cer stem cells (CRC-SCs). Bone morphogenetic protein 4 (BMP4) promotes the differentiation of normal colonic stem cells. We investigated whether BMP4 might be used to induce differentiation of CRC-SCs and for therapeutic purposes. METHODS: CRC-SCs were isolated from 25 tumor samples based on expression of CD133 or using a selection culture medium. BMP4 expression and activity on CRC-SCs were evaluated in vitro; progeny of the stem cells were evaluated by immunofluorescence, immuno- blot, and flow cytometry analyses. The potential …

Survivin is regulated by interleukin-4 in colon cancer stem cells

Colorectal cancer has provided an important model to test the stem cell hypothesis of cancer origin, which implies that cancer arises as a result of genetic aberrations in stem cells leading to deregulation of the proliferation/differentiation balance. We and others have demonstrated that, similarly to other solid tumors, colon carcinogenesis and progression are dictated by highly apoptosis-resistant stem-like cells. Our data have suggested that protection from apoptosis is achieved by autocrine production of interleukin-4 (IL-4) through up-regulation of anti-apoptotic mediators. In this study, we extend our analysis to another apoptosis inhibitor widely expressed in tumors, namely survivin…

Role of interleukin-4 on colon cancer stem cell survival

Crucial Role of Interleukin-4 in the Survival of Colon Cancer Stem Cells

Abstract Colon tumors may be maintained by a rare fraction of cancer stem-like cells (CSC) that express the cell surface marker CD133. Self-renewing CSCs exhibit relatively greater resistance to clinical cytotoxic therapies and recent work suggests that this resistance may be mediated in part by an autocrine response to the immune cytokine interleukin 4 (IL-4). Blocking IL-4 signaling can sensitize CSCs to apoptotic stimuli and increase the in vivo efficacy of cytotoxic therapy. These findings suggest that inhibitors of IL-4 signaling may offer a new therapeutic tool in colon carcinoma. [Cancer Res 2008;68(11):4022–5]

MUC1 oncoprotein promotes refractoriness to chemotherapy in thyroid cancer cells.

Abstract Overexpression of MUC1 oncoprotein is frequently observed in cancer and contributes to confer resistance to genotoxic agents. Papillary, follicular, and anaplastic thyroid carcinomas are the three forms of thyroid epithelial cancer. Anaplastic tumors are less differentiated and extremely aggressive, characterized by a poor prognosis. Little is known about the role of MUC1 in thyroid cancer. We recently showed that autocrine production of interleukin (IL)-4 and IL-10 controls thyroid cancer cell survival, growth, and resistance to chemotherapy through activation of Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) and phosphatidylinositide 3′-OH ki…

Evidences of cervical cancer stem cells derived from established cell lines.

According to the longstanding “clonal evolution” model of carcinogenesis, cervical carcinoma has long been described as a consequence of unlimited and uncontrolled cellular proliferation conferred by multiple genetic and/or epigenetic mutations that can hit any somatic cells within the tissue. However, in the last few years, accumulating evidence has suggested that the capacity of initiating a tumor, including cervical carcinoma, is rather a unique feature of a small subset of stemlike cells called “cancer stem cells” (CSCs) or “tumor-initiating cells.” CSCs have the exclusive ability to self-renew expanding the CSCs pool, and to maintain the tumor differentiating into the heterogeneous non…

Apoptosis resistance in epithelial tumors is mediated by tumor-cell-derived interleukin-4

We investigated the mechanisms involved in the resistance to cell death observed in epithelial cancers. Here, we identify that primary epithelial cancer cells from colon, breast and lung carcinomas express high levels of the antiapoptotic proteins PED, cFLIP, Bcl-xL and Bcl-2. These cancer cells produced interleukin-4 (IL-4), which amplified the expression levels of these antiapoptotic proteins and prevented cell death induced upon exposure to TRAIL or other drug agents. IL-4 blockade resulted in a significant decrease in the growth rate of epithelial cancer cells and sensitized them, both in vitro and in vivo, to apoptosis induction by TRAIL and chemotherapy via downregulation of the antia…