The influence of the microenvironment on the malignant phenotype

Park, Catherine C.; Bissell, Mina J.; Barcellos‐Hoff, Mary Helen

doi:10.1016/s1357-4310(00)01756-1

Cited by 368 publications

(278 citation statements)

References 37 publications

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“…Tumor invasion can be viewed as a deregulation in the proper sorting of cell populations, causing an alteration of normal tissue boundaries (Brown et al, 1999;Hanahan and Weinberg, 2000;Park et al, 2000). It is generally accepted that physiological and malignant invasion use similar molecular mechanisms (Liotta et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

et al. 2009

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SNAI1, ZEB1, E-cadherin (CDH1), and vitamin D receptor (VDR) genes regulate the epithelial-mesenchymal transition (EMT) that initiates the invasion process of many tumor cells. We hypothesized that this process could also affect the behavior of normal cells adjacent to the tumor. To verify this hypothesis, the expression level of these genes was determined by quantitative RT-PCR in tumor, normal adjacent, and normal distant tissues from 32 colorectal cancer (CC) patients. In addition, we extended the study to human HaCaT normal keratinocytes and SW480-ADH colon cancer cells co-cultured with SW480-ADH cells overexpressing the mouse Snai1 gene. Of 18 CC cases with SNAI1 expression in tumor tissue, five also had SNAI1 in normal adjacent tissue (NAT). Expression of SNAI1 in tumor tissue correlated with downregulation of CDH1 and VDR genes in both tumor (P ¼ 0.047 and P ¼ 0.014, respectively) and NAT lacking SNAI1 expression (P ¼ 0.054 and P ¼ 0.003). ZEB1 expression was directly related to VDR expression in tumor tissue (r ¼ 0.39; P ¼ 0.027) and inversely to CDH1 in NAT (r ¼ À0.46; P ¼ 0.010). CDH1 and VDR were also downregulated in SW480-ADH and MaCaT cells, respectively, when they were co-cultured with Snai1-expressing cells. Furthermore, cytokine analysis showed differences in the conditioned media obtained from the two cell types. These results indicate that histologically normal tissue adjacent to tumor tissue expressing the EMT-inducing gene SNAI1 shows alterations in the expression of epithelial differentiation genes such as CDH1 and VDR.

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Section: Discussionmentioning

confidence: 99%

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

et al. 2009

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“…What else is required for the development of cancer? 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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“…These changes render the fibroblasts "permissive", actively promoting tumor cell growth and allowing the tumors to lose contact inhibition and become invasive (Mareel and Leroy, 2003). As the tumor cells gain greater access to the mesenchymal stroma (Bhowmick et al, 2004;Park et al, 2000), the basement membrane is concurrently degraded (Amenta et al, 2003;Yang et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells

et al. 2008

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Recent studies have emphasized the importance of cellular microenvironment in modulating cell growth and signaling. In vitro, collagen matrices, Matrigel, and other synthetic support systems have been used to simulate in vivo microenvironments, and epithelial cells grown in these matrices manifest significant differences in proliferation, differentiation, response to drugs, and other parameters. However, these substrates do not closely resemble the mesenchymal microenvironment that is typically associated with advanced carcinomas in vivo, which is produced to a large extent by fibroblasts. In this study, we have evaluated the ability of a fibroblast-derived three-dimensional matrix to regulate the growth of a panel of 11 human tumor epithelial cell lines. Although proliferative and morphological responses to three-dimensional cues segregated independently, general responsiveness to the matrix correlated with the ability of matrix to influence drug responses. Fibroblast-derived three-dimensional matrix increased β1-integrin-dependent survival of a subset of human cancer cell lines during taxol treatment, while it sensitized or minimally influenced survival of other cells. β1-integrin-dependent changes in cell resistance to taxol did not correlate with degree of modulation of FAK and Akt, implying additional signaling factors are involved. Based on these results, we propose these matrices potentially have value as in vitro drug screening platforms.

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The influence of the microenvironment on the malignant phenotype

Cited by 368 publications

References 37 publications

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue

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

Fibroblast-derived 3D matrix differentially regulates the growth and drug-responsiveness of human cancer cells

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