Transforming growth factor-beta2 is a molecular determinant for site-specific melanoma metastasis in the brain.
Murine melanomas produce site-specific experimental brain metastases that reflect clinical reality. When injected into the internal carotid artery of mice, K-1735 melanoma cells produce metastatic lesions only in the brain parenchyma, whereas B16 melanoma cells and the somatic hybrid cells of B16 x K-1735 melanoma cells produce metastatic lesions only in the leptomeninges and ventricles. In the present study, we identified transforming growth factor-beta2 (TGF-beta2), an isoform of the TGF-beta family, as a molecular determinant of melanoma cell growth in the brain parenchyma. We found that the TGF-beta2 mRNA was highly expressed by the K-1735 cells, whereas the B16 cells or any B16 x K-1735 somatic cell-cell fusion hybrids have low expression. Transfection of the TGF-beta2 gene into B16 cells resulted in the production of microscopic metastatic lesions in the brain parenchyma, without a decrease in metastasis to the leptomeninges or ventricles. TGF-beta2 knockdown in the K-1735 melanoma cells significantly reduced metastasis to the brain parenchyma but did not induce metastasis to the leptomeninges or ventricles. These data show that TGF-beta2 expression by murine melanoma cells is necessary for the establishment and growth of metastases in the brain parenchyma.
Zhang
Chenyu
C
Department of Cancer Biology, Cancer Metastasis Research Center, The University of Texas MD Anderson Cancer Center, Houston, Texas 77230-1429, USA.
Zhang
Fahao
F
Tsan
Rachel
R
Fidler
Isaiah J
IJ
D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection; D053781:Transforming Growth Factor beta2 / Q000096:biosynthesis* / Q000235:genetics
D012333:RNA, Messenger; D034741:RNA, Small Interfering; D053781:Transforming Growth Factor beta2