Unexpected contribution of lymphatic vessels to promotion of distant metastatic tumor spread.
Unexpected contribution of lymphatic vessels to promotion of distant metastatic tumor spread.
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DOI：
10.1126/sciadv.aat4758
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发表时间：
2018-08
期刊：
影响因子：
13.6
通讯作者：
Detmar M
中科院分区：
文献类型：
--
作者：
Ma Q;Dieterich LC;Ikenberg K;Bachmann SB;Mangana J;Proulx ST;Amann VC;Levesque MP;Dummer R;Baluk P;McDonald DM;Detmar M
淋巴管除了介导肿瘤细胞从原发部位播散外，还促进器官间转移。在几种类型的癌症中，肿瘤淋巴管生成伴随着较高的前哨淋巴结转移发生率和较短的总生存期。我们询问肿瘤淋巴管生成是否也可能发生在已建立转移的远处器官中，以及它是否可能促进这些转移到其他器官的进一步转移扩散。利用小鼠肺转移模型，我们发现远处肺转移瘤发生淋巴管生成，一些转移瘤细胞位于淋巴管和引流淋巴结。在黑色素瘤患者的转移肺中，转移灶内和周围较高的淋巴密度和淋巴浸润与不良结局相关。使用转基因小鼠模型与诱导表达的血管内皮生长因子C（VEGF-C）在肺中，我们发现更大的增长肺转移，更丰富的传播到其他器官。我们的研究结果揭示了在远处器官中的肿瘤抑制剂对促进转移瘤生长及其进一步扩散到其他器官的意想不到的贡献，对转移性癌症患者的辅助治疗具有潜在的临床意义。
Lymphatic vessels promote organ-to-organ metastasis in addition to mediating tumor cell dissemination from the primary site. Tumor lymphangiogenesis is accompanied by a higher incidence of sentinel lymph node metastasis and shorter overall survival in several types of cancer. We asked whether tumor lymphangiogenesis might also occur in distant organs with established metastases and whether it might promote further metastatic spread of those metastases to other organs. Using mouse metastasis models, we found that lymphangiogenesis occurred in distant lung metastases and that some metastatic tumor cells were located in lymphatic vessels and draining lymph nodes. In metastasis-bearing lungs of melanoma patients, a higher lymphatic density within and around metastases and lymphatic invasion correlated with poor outcome. Using a transgenic mouse model with inducible expression of vascular endothelial growth factor C (VEGF-C) in the lung, we found greater growth of lung metastases, with more abundant dissemination to other organs. Our findings reveal unexpected contributions of lymphatics in distant organs to the promotion of growth of metastases and their further spread to other organs, with potential clinical implications for adjuvant therapies in patients with metastatic cancer.
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影响因子：
8.8
作者：
Ino Y;Yamazaki-Itoh R;Shimada K;Iwasaki M;Kosuge T;Kanai Y;Hiraoka N
通讯作者：
Hiraoka N
影响因子：
20.3
作者：
Hirakawa, Satoshi;Brown, Lawrence F.;Detmar, Michael
通讯作者：
Detmar, Michael
DOI：
10.1056/nejmoa1613210
发表时间：
2017-06-08
期刊：
The New England journal of medicine
影响因子：
--
作者：
Faries MB;Thompson JF;Cochran AJ;Andtbacka RH;Mozzillo N;Zager JS;Jahkola T;Bowles TL;Testori A;Beitsch PD;Hoekstra HJ;Moncrieff M;Ingvar C;Wouters MWJM;Sabel MS;Levine EA;Agnese D;Henderson M;Dummer R;Rossi CR;Neves RI;Trocha SD;Wright F;Byrd DR;Matter M;Hsueh E;MacKenzie-Ross A;Johnson DB;Terheyden P;Berger AC;Huston TL;Wayne JD;Smithers BM;Neuman HB;Schneebaum S;Gershenwald JE;Ariyan CE;Desai DC;Jacobs L;McMasters KM;Gesierich A;Hersey P;Bines SD;Kane JM;Barth RJ;McKinnon G;Farma JM;Schultz E;Vidal-Sicart S;Hoefer RA;Lewis JM;Scheri R;Kelley MC;Nieweg OE;Noyes RD;Hoon DSB;Wang HJ;Elashoff DA;Elashoff RM
通讯作者：
Elashoff RM
影响因子：
3.7
作者：
Jurisic G;Iolyeva M;Proulx ST;Halin C;Detmar M
通讯作者：
Detmar M
影响因子：
8
作者：
Baluk, Peter;Yao, Li-Chin;McDonald, Donald M.
通讯作者：
McDonald, Donald M.