Cancer-Associated Fibroblasts Enhance the Gland-Forming Capability of Prostate Cancer Stem Cells

Liao, Chun-Peng; Adisetiyo, Helty; Liang, Mengmeng; Roy-Burman, Pradip

doi:10.1158/0008-5472.can-09-3982

Cited by 103 publications

(107 citation statements)

References 40 publications

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“…Analysis of tumour-forming ability and spontaneous lung metastasis formation after contact with CAFs revealed that the activated stroma contributes to generate a population of prostate cancer stem cells with defined ability to form primary tumours and distant metastases [23]. In keeping with this, in a conditional Pten deletion mouse model of prostate adenocarcinoma, CAFs confirm their key role in the regulation of stemness properties as they enhance spheroid formation and prostate glandular structures with lesions, high proliferative index and tumour-like histopathology [90].…”

Section: Regulation Of Motility and Stemnessmentioning

confidence: 57%

Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression

Cirri

Chiarugi

2011

Cancer Metastasis Rev

491

400

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Several recent papers have now provided compelling experimental evidence that the progression of tumours towards a malignant phenotype does not depend exclusively on the cell-autonomous properties of cancer cells themselves but is also deeply influenced by tumour stroma reactivity, thereby undergoing a strict environmental control. Tumour microenvironmental elements include structural components such as the extracellular matrix or hypoxia as well as stromal cells, either resident cells or recruited from circulating precursors, as macrophages and other inflammatory cells, endothelial cells and cancer-associated fibroblasts (CAFs). All these elements synergistically play a specific role in cancer progression. This review summarizes our current knowledge on the role of CAFs in tumour progression, with a particular focus on the biunivocal interplay between CAFs and cancer cells leading to the activation of the epithelial-mesenchymal transition programme and the achievement of stem cell traits, as well as to the metabolic reprogramming of both stromal and cancer cells. Recent advances on the role of CAFs in the preparation of metastatic niche, as well as the controversial origin of CAFs, are discussed in light of the new emerging therapeutic implications of targeting CAFs.

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Section: Regulation Of Motility and Stemnessmentioning

confidence: 57%

Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression

Cirri

Chiarugi

2011

Cancer Metastasis Rev

491

400

View full text Add to dashboard Cite

show abstract

“…As for the involvement of the CAF-mediated culturing condition of CSCs, established CAFs enriched self-renewal, spheroid-forming and multipotential differentiation in Lin– SCA-1+ CD49f+ prostate CSCs [48]. However, we show that BM-MSC mediated the restoration of CD133+ MKN-7 cells, resulting in higher tumorigenicity and pluripotency.…”

Section: Discussionmentioning

confidence: 74%

Mesenchymal Stem Cells Provide an Advantageous Tumor Microenvironment for the Restoration of Cancer Stem Cells

Nishimura

Semba²,

Aoyagi³

et al. 2012

Pathobiology

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Objective: Accumulating evidences suggest that cancer-associated fibroblasts are provided from bone-marrow-derived mesenchymal stem cells (BM-MSCs); however, little is known about the mechanism(s) by which BM-MSCs accelerate cancer aggressiveness. Methods: Gastric carcinoma (GC)-derived MKN-7 cells were cocultured with UE6E7T-12 BM-MSCs. The gene expression profile in MKN-7 cells was investigated by microarray analysis. Between two major types of GCs (intestinal- and diffuse-type), the expression of genes was detected by immunohistochemistry. Results: We found that direct attachment to UE6E7T-12 induced proliferation and cluster formation of MKN-7 cells. Coculture with UE6E7T-12 increased the population of CD133+ MKN-7 cells in vitro and coimplantation of these in mice resulted in subcutaneous tumors in vivo. The wingless-type MMTV integration site (WNT) family member 5A (WNT5A) and transforming growth factor-β (TGF-β)-induced (TGFBI) genes were found to be upregulated in MKN-7 cells directly attached to UE6E7T-12. Recruitment of CD271+ BM-MSC was detected preferentially in the stroma of the diffuse-type GC and this type of GC cell also showed frequent expression of WNT5A, TGF-β type I receptor and CD133. Conclusion: BM-MSC-mediated activations of the WNT and TGF-β signaling pathways were thought to provide advantageous microenvironments for cancer progression by supporting the reacquisition and maintenance of cancer stem cells.

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“…4B). Nor does it disagree with the fact that CD133 þ isolates cancer repopulating cells within the tumor itself [12,27,31]. It does, however, raise the possibility that normal stem cells and cells of origin of cancer, within the basal compartment, are not necessarily the same cells, and the latter may involve rapidly proliferating or transient-amplifying cells within the basal cell fraction, as was originally postulated by Vander Griend et al [27].…”

Section: Discussionmentioning

confidence: 91%

Human Epithelial Basal Cells Are Cells of Origin of Prostate Cancer, Independent of CD133 Status

et al. 2012

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Normal prostatic epithelium is composed of basal and luminal cells. Prostate cancer can be initiated in both benign basal and luminal stem cells, but because basal cell markers are not expressed in patient tumors, the former result was unexpected. Since the cells of origin of prostate cancer are important therapeutic targets, we sought to provide further proof that basal stem cells have tumorigenic potential. Prostatic basal cells were enriched based on a2b1integrin hi expression and further enriched for stem cells using CD133 in nontumorigenic BPH-1 cells. Human embryonic stem cells (hESCs) were also used as a source of normal stem cells. To test their tumorigenicity, we used two alternate stromal-based approaches; (a) recombination with human cancer-associated fibroblasts (CAFs) or (b) recombination with embryonic stroma (urogenital mesenchyme) and treated host mice with testosterone and 17b-estradiol. Enriched a2b1integrin hi basal cells from BPH-1 cells resulted in malignant tumor formation using both assays of tumorigenicity. Surprisingly, the tumorigenic potential did not reside in the CD133 1 stem cells but was consistently observed in the CD133 2 population. CAFs also failed to induce prostatic tumors from hESCs. These data confirmed that benign human basal cells include cells of origin of prostate cancer and reinforced their importance as therapeutic targets. In addition, our data suggested that the more proliferative CD133 2 basal cells are more susceptible to tumorigenesis compared to the CD133 1 -enriched stem cells. These findings challenge the current dogma that normal stem cells and cells of origin of cancer are the same cell type(s).

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Cancer-Associated Fibroblasts Enhance the Gland-Forming Capability of Prostate Cancer Stem Cells

Cited by 103 publications

References 40 publications

Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression

Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression

Mesenchymal Stem Cells Provide an Advantageous Tumor Microenvironment for the Restoration of Cancer Stem Cells

Human Epithelial Basal Cells Are Cells of Origin of Prostate Cancer, Independent of CD133 Status

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