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Decoding melanoma metastasis.

Damsky WE, Rosenbaum LE, Bosenberg M - Cancers (Basel) (2010)

Bottom Line: Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma.Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process.Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA. marcus.bosenberg@yale.edu.

ABSTRACT
Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

No MeSH data available.


Related in: MedlinePlus

Steps in Melanoma Metastasis. After formation of a primary tumor, melanoma cells are thought to enter into lymphatic vessels, traverse to the lymph node, and subsequently enter into systemic circulation via the thoracic duct. After reaching systemic circulation, cells must adhere to the microvasculature of a target organ, extravasate, and subsequently proliferate in order to form a clinically relevant metastasis. The mechanisms regulating either success or failure at any step are likely important and probably differ amongst different melanomas and different target organs.
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f2-cancers-03-00126: Steps in Melanoma Metastasis. After formation of a primary tumor, melanoma cells are thought to enter into lymphatic vessels, traverse to the lymph node, and subsequently enter into systemic circulation via the thoracic duct. After reaching systemic circulation, cells must adhere to the microvasculature of a target organ, extravasate, and subsequently proliferate in order to form a clinically relevant metastasis. The mechanisms regulating either success or failure at any step are likely important and probably differ amongst different melanomas and different target organs.

Mentions: Given that metastasis is a complex process, it is not surprising that individual tumor cells may be better than others in carrying out this process. In order for a tumor cell to metastasize and form a clinically detectable and potentially lethal metastasis, it must complete a series of steps (Figure 2). After primary tumor formation, tumor cells must gain access to systemic circulation in order to spread to distant sites. In melanoma, this is thought to occur primarily by entry of tumor cells into a lymphatic vessel, transit through a lymph node, and entry into systemic circulation via the thoracic duct [33]. Once in circulation, the tumor cells must not only survive but must also adhere to an endothelium within a target organ. After adhering, tumor cells must extravasate into the parenchyma of the target organs. Here, the tumor cells find themselves in foreign microenvironments in which they must survive. If they survive, in order for clinically detectable disease to form, the cells must find a way to proliferate. In many cancers, including melanoma, clinically apparent metastases are primarily found only within a subset of organs, suggesting that something inherent to different organs may facilitate growth at these sites.


Decoding melanoma metastasis.

Damsky WE, Rosenbaum LE, Bosenberg M - Cancers (Basel) (2010)

Steps in Melanoma Metastasis. After formation of a primary tumor, melanoma cells are thought to enter into lymphatic vessels, traverse to the lymph node, and subsequently enter into systemic circulation via the thoracic duct. After reaching systemic circulation, cells must adhere to the microvasculature of a target organ, extravasate, and subsequently proliferate in order to form a clinically relevant metastasis. The mechanisms regulating either success or failure at any step are likely important and probably differ amongst different melanomas and different target organs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756353&req=5

f2-cancers-03-00126: Steps in Melanoma Metastasis. After formation of a primary tumor, melanoma cells are thought to enter into lymphatic vessels, traverse to the lymph node, and subsequently enter into systemic circulation via the thoracic duct. After reaching systemic circulation, cells must adhere to the microvasculature of a target organ, extravasate, and subsequently proliferate in order to form a clinically relevant metastasis. The mechanisms regulating either success or failure at any step are likely important and probably differ amongst different melanomas and different target organs.
Mentions: Given that metastasis is a complex process, it is not surprising that individual tumor cells may be better than others in carrying out this process. In order for a tumor cell to metastasize and form a clinically detectable and potentially lethal metastasis, it must complete a series of steps (Figure 2). After primary tumor formation, tumor cells must gain access to systemic circulation in order to spread to distant sites. In melanoma, this is thought to occur primarily by entry of tumor cells into a lymphatic vessel, transit through a lymph node, and entry into systemic circulation via the thoracic duct [33]. Once in circulation, the tumor cells must not only survive but must also adhere to an endothelium within a target organ. After adhering, tumor cells must extravasate into the parenchyma of the target organs. Here, the tumor cells find themselves in foreign microenvironments in which they must survive. If they survive, in order for clinically detectable disease to form, the cells must find a way to proliferate. In many cancers, including melanoma, clinically apparent metastases are primarily found only within a subset of organs, suggesting that something inherent to different organs may facilitate growth at these sites.

Bottom Line: Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma.Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process.Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Yale School of Medicine, New Haven, Connecticut, USA. marcus.bosenberg@yale.edu.

ABSTRACT
Metastasis accounts for the vast majority of morbidity and mortality associated with melanoma. Evidence suggests melanoma has a predilection for metastasis to particular organs. Experimental analyses have begun to shed light on the mechanisms regulating melanoma metastasis and organ specificity, but these analyses are complicated by observations of metastatic dormancy and dissemination of melanocytes that are not yet fully malignant. Additionally, tumor extrinsic factors in the microenvironment, both at the site of the primary tumor and the site of metastasis, play important roles in mediating the metastatic process. As metastasis research moves forward, paradigms explaining melanoma metastasis as a step-wise process must also reflect the temporal complexity and heterogeneity in progression of this disease. Genetic drivers of melanoma as well as extrinsic regulators of disease spread, particularly those that mediate metastasis to specific organs, must also be incorporated into newer models of melanoma metastasis.

No MeSH data available.


Related in: MedlinePlus