Decoding Melanoma Metastasis

Damsky, William; Rosenbaum, Lara E.; Bosenberg, Marcus

doi:10.3390/cancers3010126

Cited by 176 publications

(161 citation statements)

References 247 publications

(271 reference statements)

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“…The lungs are the most common site for melanoma metastases [47]. Injection of B16 cells through the lateral tail vein results in pulmonary metastasis in C57BL/6 animals.…”

Section: Resultsmentioning

confidence: 99%

Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis

et al. 2016

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Cancer development and progression to metastasis is a complex process, which largely depends on bidirectional communication between tumor cells and their microenvironment. Melanoma differentiation associated gene-9 (mda-9, also known as Syntenin-1, SDCBP), a gene first cloned by our group, is robustly expressed in multiple cancers including melanoma and contributes to invasion and metastasis in a tumor cell-intrinsic manner. However, the role of MDA-9/Syntenin in the tumor cell-extrinsic microenvironment remains unclear even though MDA-9/Syntenin is ubiquitously expressed in most organs that are active metastatic sites for melanoma, e.g., lung, lymph node, brain, and liver. In this study, we explored the effect of environmental mda-9/syntenin expression on melanoma growth and metastasis using multiple immunocompetent animal models, syngeneic B16 xenograft and intravenous B16 mouse model and a genetically engineered mouse (GEM) model of melanoma. Host-deficient expression of mda-9/syntenin in mice negatively impacted on subcutaneously implanted B16 tumor growth and lung metastasis. Absence of MDA-9/Syntenin in the lung microenvironment suppressed tumor growth by modulating in situ Interleukin 17A (IL17A) expression and impaired the recruitment of myeloid derived suppressor cells (MDSCs) and Th17 cells as compared to genetically wild type animals. Additionally, loss of mda-9/syntenin expression in a spontaneous melanoma model (melanocyte-specific pten loss and BrafV600E mutation) significantly delayed tumor initiation and suppressed metastasis to the lymph nodes and lungs. The present study highlights a novel role of mda-9/syntenin in tumor-promoting inflammation and immune suppression. These observations along with other documented roles of MDA-9/Syntenin in cancer and metastasis support the potential relevance of MDA-9/Syntenin in the carcinogenic process and as a target for developing improved therapies by using either genetic or pharmacologic approaches to treat and prevent melanoma and other cancers.

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“…The lungs are the most common site for melanoma metastases [47]. Injection of B16 cells through the lateral tail vein results in pulmonary metastasis in C57BL/6 animals.…”

Section: Resultsmentioning

confidence: 99%

Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis

et al. 2016

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“…However, other organs, such as the brain, lack endothelial porosity yet are common sites for metastases such as melanoma. These observations make it clear that purely anatomic location cannot be responsible for the distribution of metastasis to selected sites [42]. …”

Section: Progression From the Primary Site To The Metastatic Deposit:mentioning

confidence: 99%

“…The CCR7 receptor has been shown to be present on melanoma cells and has been clearly shown to result in melanoma cell migration when exposed to the receptor [42, 45, 46]. Furthermore, CXCL12, in addition to CCL21, is another ligand that interacts also with CCR4 found on melanoma cells.…”

Section: Progression From the Primary Site To The Metastatic Deposit:mentioning

confidence: 99%

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Progression of cutaneous melanoma: implications for treatment

Leong

Mihm

Murphy

et al. 2012

Clin Exp Metastasis

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The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials.

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“…The most frequent sites of visceral metastases are the lung, liver, bone, and brain (Damsky et al 2010; Tas 2012). An interesting observation is that the one-year survival was higher when the only site of visceral metastases was lung compared to other visceral metastases (Tas 2012).…”

Section: ) Introductionmentioning

confidence: 99%

Challenges in the Delivery of Therapies to Melanoma Brain Metastases

et al. 2016

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Brain metastases are a major cause of morbidity and mortality in patients with advanced melanoma. Recent approval of several molecularly-targeted agents and biologics has brought hope to patients with this previously untreatable disease. However, patients with symptomatic melanoma brain metastases have often been excluded from pivotal clinical trials. This may be in part attributed to the fact that several of the approved small molecule molecularly-targeted agents are substrates for active efflux at the blood-brain barrier, limiting their effective delivery to brain metastases. We believe that successful treatment of melanoma brain metastases will depend on the ability of these agents to traverse the blood-brain barrier and reach micrometastases that are often not clinically detectable. Moreover, overcoming the emergence of a unique pattern of resistance, possibly through adequate delivery of combination targeted therapies in brain metastases will be important in achieving a durable response. These concepts, and the current challenges in the delivery of new treatments to melanoma brain metastases, are discussed in this review.

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Decoding Melanoma Metastasis

Cited by 176 publications

References 247 publications

Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis

Knockout of MDA-9/Syntenin (SDCBP) expression in the microenvironment dampens tumor-supporting inflammation and inhibits melanoma metastasis

Progression of cutaneous melanoma: implications for treatment

Challenges in the Delivery of Therapies to Melanoma Brain Metastases

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