Tumor-derived microvesicles modulate the establishment of metastatic melanoma in a phosphatidylserine-dependent manner
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作者:
Lima, Luize G.
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Univ Fed Rio de Janeiro, Inst Med Biochem, BR-21941 Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Med Biochem, BR-21941 Rio De Janeiro, Brazil
Lima, Luize G.
[1
]
Chammas, Roger
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Univ Sao Paulo, Sch Med, Expt Oncol Lab, BR-05508 Sao Paulo, BrazilUniv Fed Rio de Janeiro, Inst Med Biochem, BR-21941 Rio De Janeiro, Brazil
Chammas, Roger
[2
]
Monteiro, Robson Q.
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Univ Fed Rio de Janeiro, Inst Med Biochem, BR-21941 Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Med Biochem, BR-21941 Rio De Janeiro, Brazil
Monteiro, Robson Q.
[1
]
Moreira, Maria Elisabete C.
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机构:Univ Fed Rio de Janeiro, Inst Med Biochem, BR-21941 Rio De Janeiro, Brazil
Moreira, Maria Elisabete C.
Barcinski, Marcello A.
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Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05508 Sao Paulo, BrazilUniv Fed Rio de Janeiro, Inst Med Biochem, BR-21941 Rio De Janeiro, Brazil
Barcinski, Marcello A.
[3
]
机构:
[1] Univ Fed Rio de Janeiro, Inst Med Biochem, BR-21941 Rio De Janeiro, Brazil
[2] Univ Sao Paulo, Sch Med, Expt Oncol Lab, BR-05508 Sao Paulo, Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, BR-05508 Sao Paulo, Brazil
Exposure of phosphatidylserine (PS) on cellular membranes and membrane-derived microvesicles stimulates a number of anti-inflammatory responses involved in malignant processes. Herein we show that B16F10 cells, a highly metastatic melanoma cell line, produce large quantities of PS-containing microvesicles in vitro. Tumor microvesicles increased TGF-beta(1) production by cultured macrophages and, in vivo, enhanced the metastatic potential of B16F10 cells in C57BL/6 mice, both effects being reversed by annexin V. Most strikingly, microvesicles induced melanoma metastasis in BALB/c mice, which are normally resistant to this tumor cell line. Altogether, this is the first demonstration that tumor-derived microvesicles favor the establishment of melanoma metastasis in a PS-dependent manner, possibly by down-regulating the host's inflammatory and/or anti-tumoral immune responses. (C) 2009 Elsevier Ireland Ltd. All rights reserved.