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Metastatic tumor dormancy in cutaneous melanoma: does surgery induce escape?

Tseng WW, Fadaki N, Leong SP - Cancers (Basel) (2011)

Bottom Line: At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed "cure" following surgical treatment of the primary tumor.The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease.Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of California at San Francisco, 513 Parnassus Avenue, Room S-321, San Francisco, CA 94143, USA. leongsx@cpmcri.org.

ABSTRACT
According to the concept of tumor dormancy, tumor cells may exist as single cells or microscopic clusters of cells that are clinically undetectable, but remain viable and have the potential for malignant outgrowth. At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed "cure" following surgical treatment of the primary tumor. The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease. In this review, we aim to demonstrate that metastatic tumor dormancy does exist in cutaneous melanoma based on evidence from mouse models and clinical observations of late recurrence and occult transmission by organ transplantation. Experimental data underscores the critical role of impaired angiogenesis and immune regulation as major mechanisms for maintenance of tumor dormancy. Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.

No MeSH data available.


Related in: MedlinePlus

Surgery and other stimuli may affect angiogenesis and immune regulation, which in combination with other local microenvironment factors (e.g., pre-metastatic niche cells), promote escape from tumor dormancy leading to tumor cell proliferation (green). The relationship of dormant tumor cells to cancer stem cells (CSC) remains to be elucidated.
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f2-cancers-03-00730: Surgery and other stimuli may affect angiogenesis and immune regulation, which in combination with other local microenvironment factors (e.g., pre-metastatic niche cells), promote escape from tumor dormancy leading to tumor cell proliferation (green). The relationship of dormant tumor cells to cancer stem cells (CSC) remains to be elucidated.

Mentions: Whether CSCs or non-CSCs constitute dormant tumor cells, the impact of the local microenvironment remains a key issue that needs to be revisited. In melanoma, a popular mouse model, B16, has been utilized to study a unique concept in metastasis known as the “pre-metastatic niche” [86,87], which in our mind, may have important implications in tumor dormancy. As first described by Kaplan et al. in the setting of lung metastasis [86], the pre-metastatic niche consists of the host cells that are present in (e.g., fibroblasts) or recruited to (e.g., bone marrow-derived hematopoietic cells) a future, distant metastatic site. These host niche cells are thought to prepare the local microenvironment for subsequent tumor cell implantation and growth. This unique microenvironment determines the fate of the first arriving tumor cells and it is highly conceivable that this initial interaction is what drives tumor cells to proliferation versus dormancy. The pre-metastatic niche likely encompasses both angiogenesis and immune regulatory mechanisms critical to tumor dormancy; alternatively, close analysis of the niche may reveal other, novel mechanisms within the local microenvironment that impact tumor dormancy (Figure 2). The presence of a specific niche cell phenotype may also predict the presence of dormant tumor cells and serve as a surrogate method of detection.


Metastatic tumor dormancy in cutaneous melanoma: does surgery induce escape?

Tseng WW, Fadaki N, Leong SP - Cancers (Basel) (2011)

Surgery and other stimuli may affect angiogenesis and immune regulation, which in combination with other local microenvironment factors (e.g., pre-metastatic niche cells), promote escape from tumor dormancy leading to tumor cell proliferation (green). The relationship of dormant tumor cells to cancer stem cells (CSC) remains to be elucidated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756387&req=5

f2-cancers-03-00730: Surgery and other stimuli may affect angiogenesis and immune regulation, which in combination with other local microenvironment factors (e.g., pre-metastatic niche cells), promote escape from tumor dormancy leading to tumor cell proliferation (green). The relationship of dormant tumor cells to cancer stem cells (CSC) remains to be elucidated.
Mentions: Whether CSCs or non-CSCs constitute dormant tumor cells, the impact of the local microenvironment remains a key issue that needs to be revisited. In melanoma, a popular mouse model, B16, has been utilized to study a unique concept in metastasis known as the “pre-metastatic niche” [86,87], which in our mind, may have important implications in tumor dormancy. As first described by Kaplan et al. in the setting of lung metastasis [86], the pre-metastatic niche consists of the host cells that are present in (e.g., fibroblasts) or recruited to (e.g., bone marrow-derived hematopoietic cells) a future, distant metastatic site. These host niche cells are thought to prepare the local microenvironment for subsequent tumor cell implantation and growth. This unique microenvironment determines the fate of the first arriving tumor cells and it is highly conceivable that this initial interaction is what drives tumor cells to proliferation versus dormancy. The pre-metastatic niche likely encompasses both angiogenesis and immune regulatory mechanisms critical to tumor dormancy; alternatively, close analysis of the niche may reveal other, novel mechanisms within the local microenvironment that impact tumor dormancy (Figure 2). The presence of a specific niche cell phenotype may also predict the presence of dormant tumor cells and serve as a surrogate method of detection.

Bottom Line: At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed "cure" following surgical treatment of the primary tumor.The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease.Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, University of California at San Francisco, 513 Parnassus Avenue, Room S-321, San Francisco, CA 94143, USA. leongsx@cpmcri.org.

ABSTRACT
According to the concept of tumor dormancy, tumor cells may exist as single cells or microscopic clusters of cells that are clinically undetectable, but remain viable and have the potential for malignant outgrowth. At metastatic sites, escape from tumor dormancy under more favorable local microenvironmental conditions or through other, yet undefined stimuli, may account for distant recurrence after supposed "cure" following surgical treatment of the primary tumor. The vast majority of evidence to date in support of the concept of tumor dormancy originates from animal studies; however, extensive epidemiologic data from breast cancer strongly suggests that this process does occur in human disease. In this review, we aim to demonstrate that metastatic tumor dormancy does exist in cutaneous melanoma based on evidence from mouse models and clinical observations of late recurrence and occult transmission by organ transplantation. Experimental data underscores the critical role of impaired angiogenesis and immune regulation as major mechanisms for maintenance of tumor dormancy. Finally, we examine evidence for the role of surgery in promoting escape from tumor dormancy at metastatic sites in cutaneous melanoma.

No MeSH data available.


Related in: MedlinePlus