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The metastatic dichotomy between carcinomas and sarcomas is explained by differential lymphovasculogenic mimicry
Author(s) -
Barsky Sanford H,
Shott Robert,
Jones Susie,
Ostler Joe,
Mahooti Sepi,
Ye Yin
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.321.9
Subject(s) - myoepithelial cell , pathology , lymphatic system , lymphangiogenesis , stromal cell , mesenchymal stem cell , vasculogenic mimicry , cd31 , metastasis , biology , sarcoma , lymphovascular invasion , leiomyosarcoma , immunohistochemistry , medicine , cancer , genetics
Human carcinomas are known to metastasize primarily through lymphatics whereas sarcomas metastasize hematogenously. However the reason for this metastatic dichotomy is not understood. With the newly emerging experimental evidence that lymphovascular invasion (LVI) and metastasis may be regulated by local lymphovasculogenesis, we wondered whether these phenomenon might differ in carcinomas v sarcomas and account for their metastatic disparity. We examined 20 human carcinomas and 20 sarcomas as well as derived cell lines to assess their comparative degrees of lymphangiogenesis and vasculogenesis. We conducted IHC studies with lymphatic (D2‐40), vascular (CD31), proliferation (Ki‐67) and myoepithelial / mesenchymal stem cell markers singly and in combination, designed to elucidate the nature of the lymphovasculogenesis in carcinomas v sarcomas. We also studied the expression profile of VEGF members: ‐A, ‐B, ‐C, ‐D in the tumors by real time PCR. The carcinomas exhibited a much greater density of lymphatics with LVI limited to only lymphatics whereas the sarcomas exhibited a much greater density of blood vessels with LVI limited to only blood vessels. However the lymphatics and blood vessels containing tumor emboli from carcinomas v sarcomas differed from each other and the resident vasculature in expression of myoepithelial v mesenchymal stem cell markers suggesting a different stem cell origin. The sarcomas paradoxically had 50 fold greater VEGF‐C whereas the carcinomas had 3 fold greater VEGF‐A. Our findings suggest that metastatic behavior of carcinomas v sarcomas is regulated by the type of LVI which, in turn, is governed not by stromal invasion nor VEGF‐mediated lymphovasculogenesis but rather by differential lymphovasculogenic mimicry.