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Role of cancer microenvironment in metastasis: focus on colon cancer.

Gout S, Huot J - Cancer Microenviron (2008)

Bottom Line: In most cases, death will result from the formation of distal secondary sites called metastases.These mutations lead to unrestrained growth of the primary neoplasm and a propensity to detach and to progress through the subsequent steps of metastatic dissemination.This process depends tightly on the surrounding microenvironment.

View Article: PubMed Central - PubMed

Affiliation: Le Centre de recherche en cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, 9 rue McMahon, Quebec, Canada.

ABSTRACT
One person on three will receive a diagnostic of cancer during his life. About one third of them will die of the disease. In most cases, death will result from the formation of distal secondary sites called metastases. Several events that lead to cancer are under genetic control. In particular, cancer initiation is tightly associated with specific mutations that affect proto-oncogenes and tumour suppressor genes. These mutations lead to unrestrained growth of the primary neoplasm and a propensity to detach and to progress through the subsequent steps of metastatic dissemination. This process depends tightly on the surrounding microenvironment. In fact, several studies support the point that tumour development relies on a continuous cross-talk between cancer cells and their cellular and extracellular microenvironments. This signaling cross-talk is mediated by transmembrane receptors expressed on cancer cells and stromal cells. The aim of this manuscript is to review how the cancer microenvironment influences the journey of a metastatic cell taking liver invasion by colorectal cancer cells as a model.

No MeSH data available.


Related in: MedlinePlus

The epithelial–mesenchymal transition. Epithelial-to-Mesenchymal Transition (EMT) is a morphogenetic process in which epithelial cells loose their characteristics and gain mesenchymal properties during embryogenesis and during progression of cancer. Carcinoma cells acquire a mesenchymal-like state in order to facilitate their migration and invasion. The EMT process is induced and regulated by effectors such as growth factors (TGFβ, PDGF, EGF), cytokines (Il-8) and ECM components. It is characterized by loss of epithelial markers such as E-cadherin and cytokeratins and gain of mesenchymal markers such as N-cadherin and vimentin
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Fig3: The epithelial–mesenchymal transition. Epithelial-to-Mesenchymal Transition (EMT) is a morphogenetic process in which epithelial cells loose their characteristics and gain mesenchymal properties during embryogenesis and during progression of cancer. Carcinoma cells acquire a mesenchymal-like state in order to facilitate their migration and invasion. The EMT process is induced and regulated by effectors such as growth factors (TGFβ, PDGF, EGF), cytokines (Il-8) and ECM components. It is characterized by loss of epithelial markers such as E-cadherin and cytokeratins and gain of mesenchymal markers such as N-cadherin and vimentin

Mentions: Epithelial–Mesenchymal Transition Cancer cell detachment from the primary site is one of the key initial events required for metastasis. This is tightly associated with epithelial–mesenchymal transition (EMT), a morphogenetic process in which epithelial cells loose their characteristics and gain mesenchymal properties during embryogenesis [37] (Fig. 3). There is now accumulating evidence indicating that carcinoma cells usurp normal developmental EMT to detach from the primary neoplasm and migrate to distant sites. In this context, histochemical studies reveal that adenocarcinoma is accompanied by the release of single cells through EMT [38]. In particular, it appears that EMT is an integral component of colorectal cancer progression [39, 40]. One of the major elements that characterize EMT of carcinoma cells is the loss of E-cadherin-mediated cell–cell adhesion [41]. This latter event results from mutations in the E-cadherin gene, proteolytic degradation of E-cadherin, IGF1-mediated internalization of E-cadherin and disruption of the function of E-cadherin involving β-catenin [41]. Loss of E-cadherin further results from a decrease in its expression that is subsequent to promoter hypermethylation and activation of transcriptional repressors such as Snail and FOXC2 [42, 43]. In colon cancer cells, deregulation of E-cadherin and EMT is associated with a peripheral accumulation of Src and phospho-myosin and with an increased expression of the guanine nucleotide exchange factor TIAM 1 [44, 45]. Moreover, the level of RhoC varies widely in colon cancer cells and an elevated RhoC expression correlates with a poor prognostic and with an aberrant expression and localization of E-cadherin [46]. Interestingly, in melanoma, breast cancer and prostate cancer, the disruption of the E-cadherin-mediated cancer cell adhesion is associated with the so-called cadherin-switch in which the E-cadherin loss is accompanied by de novo expression of mesenchymal cadherin, such as N-cadherin. This shift is important since the loss of E-cadherin by cancer cells is associated with their inability to adhere with themselves and with normal epithelial cells. Furthermore, by up-regulating the expression of N-cadherin, cancer cells will interact with stromal cells, thereby changing their location and favoring the invasion of the surrounding stroma. Moreover, N-cadherin confers motility and migration to cancer cells [47]. Hence, the cadherin switch is an important component of the EMT that characterizes the early step of cancer progression toward an invasive and metastatic phenotype (Fig. 3).Fig. 3


Role of cancer microenvironment in metastasis: focus on colon cancer.

Gout S, Huot J - Cancer Microenviron (2008)

The epithelial–mesenchymal transition. Epithelial-to-Mesenchymal Transition (EMT) is a morphogenetic process in which epithelial cells loose their characteristics and gain mesenchymal properties during embryogenesis and during progression of cancer. Carcinoma cells acquire a mesenchymal-like state in order to facilitate their migration and invasion. The EMT process is induced and regulated by effectors such as growth factors (TGFβ, PDGF, EGF), cytokines (Il-8) and ECM components. It is characterized by loss of epithelial markers such as E-cadherin and cytokeratins and gain of mesenchymal markers such as N-cadherin and vimentin
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2654352&req=5

Fig3: The epithelial–mesenchymal transition. Epithelial-to-Mesenchymal Transition (EMT) is a morphogenetic process in which epithelial cells loose their characteristics and gain mesenchymal properties during embryogenesis and during progression of cancer. Carcinoma cells acquire a mesenchymal-like state in order to facilitate their migration and invasion. The EMT process is induced and regulated by effectors such as growth factors (TGFβ, PDGF, EGF), cytokines (Il-8) and ECM components. It is characterized by loss of epithelial markers such as E-cadherin and cytokeratins and gain of mesenchymal markers such as N-cadherin and vimentin
Mentions: Epithelial–Mesenchymal Transition Cancer cell detachment from the primary site is one of the key initial events required for metastasis. This is tightly associated with epithelial–mesenchymal transition (EMT), a morphogenetic process in which epithelial cells loose their characteristics and gain mesenchymal properties during embryogenesis [37] (Fig. 3). There is now accumulating evidence indicating that carcinoma cells usurp normal developmental EMT to detach from the primary neoplasm and migrate to distant sites. In this context, histochemical studies reveal that adenocarcinoma is accompanied by the release of single cells through EMT [38]. In particular, it appears that EMT is an integral component of colorectal cancer progression [39, 40]. One of the major elements that characterize EMT of carcinoma cells is the loss of E-cadherin-mediated cell–cell adhesion [41]. This latter event results from mutations in the E-cadherin gene, proteolytic degradation of E-cadherin, IGF1-mediated internalization of E-cadherin and disruption of the function of E-cadherin involving β-catenin [41]. Loss of E-cadherin further results from a decrease in its expression that is subsequent to promoter hypermethylation and activation of transcriptional repressors such as Snail and FOXC2 [42, 43]. In colon cancer cells, deregulation of E-cadherin and EMT is associated with a peripheral accumulation of Src and phospho-myosin and with an increased expression of the guanine nucleotide exchange factor TIAM 1 [44, 45]. Moreover, the level of RhoC varies widely in colon cancer cells and an elevated RhoC expression correlates with a poor prognostic and with an aberrant expression and localization of E-cadherin [46]. Interestingly, in melanoma, breast cancer and prostate cancer, the disruption of the E-cadherin-mediated cancer cell adhesion is associated with the so-called cadherin-switch in which the E-cadherin loss is accompanied by de novo expression of mesenchymal cadherin, such as N-cadherin. This shift is important since the loss of E-cadherin by cancer cells is associated with their inability to adhere with themselves and with normal epithelial cells. Furthermore, by up-regulating the expression of N-cadherin, cancer cells will interact with stromal cells, thereby changing their location and favoring the invasion of the surrounding stroma. Moreover, N-cadherin confers motility and migration to cancer cells [47]. Hence, the cadherin switch is an important component of the EMT that characterizes the early step of cancer progression toward an invasive and metastatic phenotype (Fig. 3).Fig. 3

Bottom Line: In most cases, death will result from the formation of distal secondary sites called metastases.These mutations lead to unrestrained growth of the primary neoplasm and a propensity to detach and to progress through the subsequent steps of metastatic dissemination.This process depends tightly on the surrounding microenvironment.

View Article: PubMed Central - PubMed

Affiliation: Le Centre de recherche en cancérologie de l'Université Laval, L'Hôtel-Dieu de Québec, 9 rue McMahon, Quebec, Canada.

ABSTRACT
One person on three will receive a diagnostic of cancer during his life. About one third of them will die of the disease. In most cases, death will result from the formation of distal secondary sites called metastases. Several events that lead to cancer are under genetic control. In particular, cancer initiation is tightly associated with specific mutations that affect proto-oncogenes and tumour suppressor genes. These mutations lead to unrestrained growth of the primary neoplasm and a propensity to detach and to progress through the subsequent steps of metastatic dissemination. This process depends tightly on the surrounding microenvironment. In fact, several studies support the point that tumour development relies on a continuous cross-talk between cancer cells and their cellular and extracellular microenvironments. This signaling cross-talk is mediated by transmembrane receptors expressed on cancer cells and stromal cells. The aim of this manuscript is to review how the cancer microenvironment influences the journey of a metastatic cell taking liver invasion by colorectal cancer cells as a model.

No MeSH data available.


Related in: MedlinePlus