Know thy neighbor: stromal cells can contribute oncogenic signals

Tlsty, Thea D.; Hein, Patrick W.

doi:10.1016/s0959-437x(00)00156-8

Cited by 387 publications

(288 citation statements)

References 32 publications

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“…Others have reported that tumors secrete factors that recruit stromal, vascular, bone marrow and other stem cells to the tumor; theoretically the recruited cells provide a scaffolding and source of nutrients. 32,33 Several chemokines are known to be secreted by tumors that may mediate the observed tropism, including vascular endothelial growth factor, transforming growth factor-b (TGF) family members, fibroblast growth factor (FGF) family members, platelet-derived growth factor family members, MCP-1, epidermal growth factor and interleukin-8. 34 Cells related to UCMS cells, bone marrow stromal cells, have been shown to exhibit a tropism for damaged or rapidly growing tissues as well as tumors.…”

Section: Discussionmentioning

confidence: 99%

Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

et al. 2007

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Umbilical cord matrix stem (UCMS) cells are unique stem cells derived from Wharton's jelly, which have been shown to express genes characteristic of primitive stem cells. To test the safety of these cells, human UCMS cells were injected both intravenously and subcutaneously in large numbers into severe combined immunodeficiency (SCID) mice and multiple tissues were examined for evidence of tumor formation. UCMS cells did not form gross or histological teratomas up to 50 days posttransplantation. Next, to evaluate whether UCMS cells could selectively engraft in xenotransplanted tumors, MDA 231 cells were intravenously transplanted into SCID mice, followed by intravenous transplantation of UCMS cells 1 and 2 weeks later. UCMS cells were found near or within lung tumors but not in other tissues. Finally, UCMS cells were engineered to express human interferon beta -designated 'UCMSÀIFN-b'. UCMSÀIFN-b cells were intravenously transplanted at multiple intervals into SCID mice bearing MDA 231 tumors and their effect on tumors was examined. UCMSÀIFN-b cells significantly reduced MDA 231 tumor burden in SCID mouse lungs indicated by wet weight. These results clearly indicate safety and usability of UCMS cells in cancer gene therapy. Thus, UCMS cells can potentially be used for targeted delivery of cancer therapeutics.

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Section: Discussionmentioning

confidence: 99%

Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

et al. 2007

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“…Several decades of cell biology have established that many cells with oncogenic mutations also require a permissive tissue microenvironment in which to progress into a malignant tumor (DePinho, 2000;Park et al, 2000;Bissell and Radisky, 2001;Liotta and Kohn, 2001;Coussens and Werb, 2002). Of particular importance for the development of epithelial tumors-the major type of age-related cancer that develops in humans-are the interactions between the epithelium and the underlying stroma (Birchmeier and Birchmeier, 1995;DePinho, 2000;Bissell and Radisky, 2001;Chrenek et al, 2001;Liotta and Kohn, 2001;Tlsty and Hein, 2001).…”

Section: Do Senescent Cells Promote Age-related Pathology?mentioning

confidence: 99%

Aging, tumor suppression and cancer: high wire-act!

Campisi

2005

Mechanisms of Ageing and Development

155

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Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responsesapoptosis or senescence-that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation. We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic pleiotropyprotecting organisms from cancer early in life, but promoting aging phenotypes, including late life cancer, in older organisms. # 2004 Published by Elsevier Ireland Ltd.

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“…A common finding in many types of solid tumours is that stromal fibroblasts become 'activated' and express a number of contractile proteins, particularly a-smooth muscle actin (SMA) (Tlsty and Hein, 2001). These cells have been referred to as peritumour fibroblasts, carcinoma-associated fibroblasts and activated stroma, but are now more commonly called myofibroblasts (MF).…”

mentioning

confidence: 99%

Tumour-derived TGF-β1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells

et al. 2004

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The development of an altered stromal microenvironment is a common feature of many tumours including squamous cell carcinoma (SCC), and there is increasing evidence that these changes in the stroma, which include increased expression of proteases and cytokines, may actually promote tumour progression. A common finding is that stromal fibroblasts become 'activated' myofibroblasts, expressing smooth muscle actin and secreting cytokines, proteases and matrix proteins. We show that myofibroblasts are commonly found in the stroma of oral SCC and are often concentrated at the invasive margin of the tumour. Using oral SCC cells and primary oral fibroblasts, we demonstrate that tumour cells directly induce a myofibroblastic phenotype, and that this transdifferentiation is dependent on SCC-derived TGF-b1. In turn, myofibroblasts secrete significantly higher levels of hepatocyte growth factor/scatter factor compared with fibroblast controls, and this cytokine promotes SCC invasion through Matrigel, a mixture of basement membrane proteins. This is the first time that this double paracrine mechanism has been demonstrated between squamous carcinoma cells and fibroblasts, and emphasises that cancer invasion can be promoted indirectly by the release of tumour-induced host factors from stroma.

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Know thy neighbor: stromal cells can contribute oncogenic signals

Cited by 387 publications

References 32 publications

Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

Development of human umbilical cord matrix stem cell-based gene therapy for experimental lung tumors

Aging, tumor suppression and cancer: high wire-act!

Tumour-derived TGF-β1 modulates myofibroblast differentiation and promotes HGF/SF-dependent invasion of squamous carcinoma cells

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