Periostin Is a Key Niche Component for Wound Metastasis of Melanoma.
Periostin Is a Key Niche Component for Wound Metastasis of Melanoma.
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DOI：
10.1371/journal.pone.0129704
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Saya H
中科院分区：
文献类型：
--
作者：
Fukuda K;Sugihara E;Ohta S;Izuhara K;Funakoshi T;Amagai M;Saya H
组织损伤促进了几种人类癌症的转移，尽管与伤口愈合相关的吸引循环肿瘤细胞的因素仍然未知。在此，我们检查了肢端雀斑样黑色素瘤患者创伤后1个月出现的原发性和转移性病变。骨膜蛋白（POSTIN），1型胶原蛋白和纤连蛋白的mRNA水平显着增加，在转移灶相对于原发灶。这些细胞外基质蛋白在伤口部位的增加在伤口愈合的小鼠模型中再现，其中Postn mRNA的上调持续时间最长。在受伤的小鼠和患者的转移性病变中，在黑色素瘤细胞巢周围的区域中表达了POST1。在体外实验中，罂粟碱可减弱黑色素瘤细胞的粘附，促进其迁移，而不影响其增殖。在小鼠模型中，伤口部位以及皮下注射的成骨细胞分泌大量的过氧化物酶，引起远处移植的黑色素瘤细胞在这些部位的转移。通过shRNA抑制POSTs的成骨细胞显示出促进这种转移的能力大大降低。我们的研究结果表明，POR4是一个关键因素，促进黑色素瘤细胞转移到伤口部位，提供了一个转移前的小生境。
Tissue injury promotes metastasis of several human cancers, although factors associated with wound healing that attract circulating tumor cells have remained unknown. Here, we examined the primary and metastatic lesions that appeared 1 month after trauma in a patient with acral lentiginous melanoma. The levels of mRNA for periostin (POSTN), type 1 collagen, and fibronectin were significantly increased in the metastatic lesion relative to the primary lesion. The increase of these extracellular matrix proteins at the wound site was reproduced in a mouse model of wound healing, with the upregulation of Postn mRNA persisting the longest. POSTN was expressed in the region surrounding melanoma cell nests in metastatic lesions of both wounded mice and the patient. POSTN attenuated the cell adhesion and promoted the migration of melanoma cells without affecting their proliferation in vitro. In the mouse model, the wound site as well as subcutaneously injected osteoblasts that secrete large amounts of POSTN invited the metastasis of remotely-transplanted melanoma cells on the sites. Osteoblasts with suppression of POSTN by shRNA showed a greatly reduced ability to promote such metastasis. Our results suggest that POSTN is a key factor in promoting melanoma cell metastasis to wound sites by providing a premetastatic niche.
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影响因子：
64.5
作者：
Roesch A;Fukunaga-Kalabis M;Schmidt EC;Zabierowski SE;Brafford PA;Vultur A;Basu D;Gimotty P;Vogt T;Herlyn M
通讯作者：
Herlyn M
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11.2
作者：
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45.3
作者：
Balch, Charles M.;Gershenwald, Jeffrey E.;Sondak, Vernon K.
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3.7
作者：
Nishiyama T;Kii I;Kashima TG;Kikuchi Y;Ohazama A;Shimazaki M;Fukayama M;Kudo A
通讯作者：
Kudo A
影响因子：
11.5
作者：
Ulmer, A;Schmidt-Kittler, O;Klein, CA
通讯作者：
Klein, CA