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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

Interaction of cancer cells with the microenvironment. Beyond genetic alterations that affect cancer cells, a dynamic interaction occurs between cancer cells and the host stromal microenvironment to support cancerous growth and dissemination. The stroma is constituted mainly of cellular elements such as fibroblasts and immune cells, and non-cellular elements such as ECM. These stromal elements act in a synergistic cross-talk with the cancer cells from the primary sites to sustain cancer growth and metastasis. For example, cancer-associated macrophages and fibroblasts influence cancer initiation/promotion by secreting cytokines, growth factors and chemokines
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Fig2: Interaction of cancer cells with the microenvironment. Beyond genetic alterations that affect cancer cells, a dynamic interaction occurs between cancer cells and the host stromal microenvironment to support cancerous growth and dissemination. The stroma is constituted mainly of cellular elements such as fibroblasts and immune cells, and non-cellular elements such as ECM. These stromal elements act in a synergistic cross-talk with the cancer cells from the primary sites to sustain cancer growth and metastasis. For example, cancer-associated macrophages and fibroblasts influence cancer initiation/promotion by secreting cytokines, growth factors and chemokines

Mentions: Influence of Stromal Cells on the Primary Neoplasm Cancer cells of the primary neoplasm constitute a histological lesion that is embedded in the stromal microenvironment of a given tissue. The tumour stroma plays an essential role in the development of colorectal cancer and is referred to as a “reactive stroma” [7]. This reactive stroma is associated with an increased number of fibroblasts, enhanced capillary density and deposition of a new ECM rich in type-1-collagen and fibrin. Macrophages are also recruited in the reactive stroma in response to the healing process generated by the tumour. There is evidence indicating that the primary neoplasm and the reactive stroma communicate in a reciprocal way via the basement membrane [7]. Moreover, several studies show that the reactive stroma influences the initiation and promotion of cancer by secreting cytokines and growth factors or by expressing their receptors (Fig. 2). For example, stromal cells within colon carcinoma express high level of PDGF receptor (PDGFR). In turn, this has a marked impact in colon cancer progression since chemical inhibition of PDGFR signaling in the stromal cells inhibits cancer progression [8]. On the other hand, several studies indicate that fibroblasts within a tumour harbor mutations that activate them into myofibroblasts or cancer associated fibroblasts (CAFs). These genetically altered fibroblasts may directly be involved in cancer initiation as demonstrated in mouse models. For example, when immortalized prostate epithelial cells are grafted in mice together with normal fibroblasts or CAFs taken from the primary site, intraepithelial neoplasia of the prostate emerge only in the presence of CAFs [9]. This clearly indicates that CAFs have the potential to initiate tumour formation. Along these lines, CAFs produce cytokines such as TGFβ that activate cancer cells and trigger their detachment from the primary neoplasm. Interestingly, a recent study showed that TGFβ also leads to the transformation of lung endothelial cells into CAFs, which favors progression of lung cancer in a mouse model. Overall, this study indicates that endothelial cells contribute to expand the pool of CAFs that synergize with cancer cells to favor their progression [10]. This important study further highlights the intricate signaling network that exists between a tumour and its environment.Fig. 2


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

Gout S, Huot J - Cancer Microenviron (2008)

Interaction of cancer cells with the microenvironment. Beyond genetic alterations that affect cancer cells, a dynamic interaction occurs between cancer cells and the host stromal microenvironment to support cancerous growth and dissemination. The stroma is constituted mainly of cellular elements such as fibroblasts and immune cells, and non-cellular elements such as ECM. These stromal elements act in a synergistic cross-talk with the cancer cells from the primary sites to sustain cancer growth and metastasis. For example, cancer-associated macrophages and fibroblasts influence cancer initiation/promotion by secreting cytokines, growth factors and chemokines
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2654352&req=5

Fig2: Interaction of cancer cells with the microenvironment. Beyond genetic alterations that affect cancer cells, a dynamic interaction occurs between cancer cells and the host stromal microenvironment to support cancerous growth and dissemination. The stroma is constituted mainly of cellular elements such as fibroblasts and immune cells, and non-cellular elements such as ECM. These stromal elements act in a synergistic cross-talk with the cancer cells from the primary sites to sustain cancer growth and metastasis. For example, cancer-associated macrophages and fibroblasts influence cancer initiation/promotion by secreting cytokines, growth factors and chemokines
Mentions: Influence of Stromal Cells on the Primary Neoplasm Cancer cells of the primary neoplasm constitute a histological lesion that is embedded in the stromal microenvironment of a given tissue. The tumour stroma plays an essential role in the development of colorectal cancer and is referred to as a “reactive stroma” [7]. This reactive stroma is associated with an increased number of fibroblasts, enhanced capillary density and deposition of a new ECM rich in type-1-collagen and fibrin. Macrophages are also recruited in the reactive stroma in response to the healing process generated by the tumour. There is evidence indicating that the primary neoplasm and the reactive stroma communicate in a reciprocal way via the basement membrane [7]. Moreover, several studies show that the reactive stroma influences the initiation and promotion of cancer by secreting cytokines and growth factors or by expressing their receptors (Fig. 2). For example, stromal cells within colon carcinoma express high level of PDGF receptor (PDGFR). In turn, this has a marked impact in colon cancer progression since chemical inhibition of PDGFR signaling in the stromal cells inhibits cancer progression [8]. On the other hand, several studies indicate that fibroblasts within a tumour harbor mutations that activate them into myofibroblasts or cancer associated fibroblasts (CAFs). These genetically altered fibroblasts may directly be involved in cancer initiation as demonstrated in mouse models. For example, when immortalized prostate epithelial cells are grafted in mice together with normal fibroblasts or CAFs taken from the primary site, intraepithelial neoplasia of the prostate emerge only in the presence of CAFs [9]. This clearly indicates that CAFs have the potential to initiate tumour formation. Along these lines, CAFs produce cytokines such as TGFβ that activate cancer cells and trigger their detachment from the primary neoplasm. Interestingly, a recent study showed that TGFβ also leads to the transformation of lung endothelial cells into CAFs, which favors progression of lung cancer in a mouse model. Overall, this study indicates that endothelial cells contribute to expand the pool of CAFs that synergize with cancer cells to favor their progression [10]. This important study further highlights the intricate signaling network that exists between a tumour and its environment.Fig. 2

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