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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 hallmarks of cancer cells. Cancer cells from most human cancers share six acquired traits that collectively dictate malignant growth: (a) self-sufficiency with respect to growth signals, (b) insensitivity to growth-inhibitory signals, (c) evasion of programmed cell death, (d) limitless replicative potential, (e) sustained angiogenesis, and (f) tissue invasion and metastasis. All these traits contribute to growth, detachment and invading potential of cancer cells (adapted from [1])
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Fig1: The hallmarks of cancer cells. Cancer cells from most human cancers share six acquired traits that collectively dictate malignant growth: (a) self-sufficiency with respect to growth signals, (b) insensitivity to growth-inhibitory signals, (c) evasion of programmed cell death, (d) limitless replicative potential, (e) sustained angiogenesis, and (f) tissue invasion and metastasis. All these traits contribute to growth, detachment and invading potential of cancer cells (adapted from [1])

Mentions: Carcinogenesis is a multistep process that results from genetic alterations that underlie the transformation of normal cells into malignant derivatives. In fact, the genome of tumour cells is altered at several sites as a result of point mutations or changes in chromosome integrity. It is now accepted that cancer arises from a succession of genetic alterations that confer growth advantages leading to the progressive conversion of normal cells into cancer cells [1]. The genetic modifications that contribute to cancer initiation and progression are regrouped within six phenotypic traits that constitute the essential hallmarks of cancer. These have been described in detail in a didactic review by Hanahan and Weinberg and are summarized in Fig. 1 [1]. Firstly, cancer cell have acquired self-sufficiency of growth through mutations that activate proto-oncogenes allowing cancer cells to generate their own growth signals such as secretion of transforming growth factor-α (TGFα) or platelet-derived growth factor (PDGF). Secondly, cancer cells are characterized by their insensitivity to antigrowth signals, in part through disruption of the Rb pathway. Thirdly, cancer cells have gained the capability to escape apoptosis through mutations that inactivate tumour suppressor genes such as p53 or PTEN, or through activation of survival pathways involving insulin-like growth factor-1/2 (IGF1/2) or interleukin-3 (IL-3). Fourthly, cancer cells have lost the cell-autonomous program that limits their multiplication. This results mainly from turning on of telomerase, an enzyme that maintains the telomeres at the end of chromosomes, thereby impairing senescence and death. Fifthly, the growing neoplasm becomes capable to sustain its oxygen and nutritive supplies by promoting angiogenesis. This neovascularization process is turned on by the expression of pro-angiogenic agents such as vascular endothelial growth factor (VEGF) produced by cancer cells or by the repression of anti-angiogenic processes such as a fall in thrombospondin levels. Sixthly, cells from the primary neoplasm detach from this site to invade adjacent tissues and travel to distant sites that they will colonize to form metastases. Recent studies have indicated that during the acquisition of these inherent hallmarks, the cancer cells need to interact synergistically with their surrounding microenvironment to form a neoplasm and to progress further to colonize distant organs. This review will focus on the major cancer cell-microenvironment interactions that pave the journey of a metastatic cell from the primary site to the metastatic site, taking the invasion of the liver by colorectal cancer cells as a model.Fig. 1


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

Gout S, Huot J - Cancer Microenviron (2008)

The hallmarks of cancer cells. Cancer cells from most human cancers share six acquired traits that collectively dictate malignant growth: (a) self-sufficiency with respect to growth signals, (b) insensitivity to growth-inhibitory signals, (c) evasion of programmed cell death, (d) limitless replicative potential, (e) sustained angiogenesis, and (f) tissue invasion and metastasis. All these traits contribute to growth, detachment and invading potential of cancer cells (adapted from [1])
© Copyright Policy
Related In: Results  -  Collection

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

Fig1: The hallmarks of cancer cells. Cancer cells from most human cancers share six acquired traits that collectively dictate malignant growth: (a) self-sufficiency with respect to growth signals, (b) insensitivity to growth-inhibitory signals, (c) evasion of programmed cell death, (d) limitless replicative potential, (e) sustained angiogenesis, and (f) tissue invasion and metastasis. All these traits contribute to growth, detachment and invading potential of cancer cells (adapted from [1])
Mentions: Carcinogenesis is a multistep process that results from genetic alterations that underlie the transformation of normal cells into malignant derivatives. In fact, the genome of tumour cells is altered at several sites as a result of point mutations or changes in chromosome integrity. It is now accepted that cancer arises from a succession of genetic alterations that confer growth advantages leading to the progressive conversion of normal cells into cancer cells [1]. The genetic modifications that contribute to cancer initiation and progression are regrouped within six phenotypic traits that constitute the essential hallmarks of cancer. These have been described in detail in a didactic review by Hanahan and Weinberg and are summarized in Fig. 1 [1]. Firstly, cancer cell have acquired self-sufficiency of growth through mutations that activate proto-oncogenes allowing cancer cells to generate their own growth signals such as secretion of transforming growth factor-α (TGFα) or platelet-derived growth factor (PDGF). Secondly, cancer cells are characterized by their insensitivity to antigrowth signals, in part through disruption of the Rb pathway. Thirdly, cancer cells have gained the capability to escape apoptosis through mutations that inactivate tumour suppressor genes such as p53 or PTEN, or through activation of survival pathways involving insulin-like growth factor-1/2 (IGF1/2) or interleukin-3 (IL-3). Fourthly, cancer cells have lost the cell-autonomous program that limits their multiplication. This results mainly from turning on of telomerase, an enzyme that maintains the telomeres at the end of chromosomes, thereby impairing senescence and death. Fifthly, the growing neoplasm becomes capable to sustain its oxygen and nutritive supplies by promoting angiogenesis. This neovascularization process is turned on by the expression of pro-angiogenic agents such as vascular endothelial growth factor (VEGF) produced by cancer cells or by the repression of anti-angiogenic processes such as a fall in thrombospondin levels. Sixthly, cells from the primary neoplasm detach from this site to invade adjacent tissues and travel to distant sites that they will colonize to form metastases. Recent studies have indicated that during the acquisition of these inherent hallmarks, the cancer cells need to interact synergistically with their surrounding microenvironment to form a neoplasm and to progress further to colonize distant organs. This review will focus on the major cancer cell-microenvironment interactions that pave the journey of a metastatic cell from the primary site to the metastatic site, taking the invasion of the liver by colorectal cancer cells as a model.Fig. 1

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