Hyaluronan, Cancer-Associated Fibroblasts and the Tumor Microenvironment in Malignant Progression.
Hyaluronan, Cancer-Associated Fibroblasts and the Tumor Microenvironment in Malignant Progression.
复制标题
DOI：
10.3389/fcell.2018.00048
复制
发表时间：
2018
影响因子：
5.5
通讯作者：
Turley EA
中科院分区：
文献类型：
--
作者：
McCarthy JB;El-Ashry D;Turley EA
本文综述了CAFs在形成有利于肿瘤发生和扩散的“癌化”纤维化基质中的作用，特别强调了细胞外基质成分透明质酸（HA）在这些过程中的作用。肿瘤及其宿主微环境的结构复杂性现在被认为是恶性进展和治疗耐药的重要因素。这种复杂性有多个组成部分，包括细胞外基质（ECM）的广泛重塑和肿瘤基质中相关的生物力学变化。肿瘤间质常呈纤维化，富含纤维状I型胶原蛋白和透明质酸（HA）。癌症相关成纤维细胞（CAFs）是这种纤维化性ECM的主要来源。CAFs组织胶原原纤维，这些生物力学变化在CAFs的指导下或在上皮细胞向间质细胞转化（EMT）后为入侵癌细胞提供了通道。肿瘤微环境中HA代谢的增加通过多种功能指导癌的发生和传播。本文综述的HA的主要作用是在恶性前和恶性间质中激活CAFs，并通过促进CAFs和肿瘤细胞的运动促进其侵袭，从而促进其侵袭。循环CAFs （cCAFs）也与循环肿瘤细胞（CTC）形成异型簇，循环肿瘤细胞被认为是转移集落的前体。cCAFs可能是肿瘤细胞外渗和形成适合新肿瘤菌落生长的转移生态位所必需的。针对HA和CAFs设计的治疗干预措施，以限制肿瘤扩散和增加对当前治疗的反应。
This review summarizes the roles of CAFs in forming a “cancerized” fibrotic stroma favorable to tumor initiation and dissemination, in particular highlighting the functions of the extracellular matrix component hyaluronan (HA) in these processes. The structural complexity of the tumor and its host microenvironment is now well appreciated to be an important contributing factor to malignant progression and resistance-to-therapy. There are multiple components of this complexity, which include an extensive remodeling of the extracellular matrix (ECM) and associated biomechanical changes in tumor stroma. Tumor stroma is often fibrotic and rich in fibrillar type I collagen and hyaluronan (HA). Cancer-associated fibroblasts (CAFs) are a major source of this fibrotic ECM. CAFs organize collagen fibrils and these biomechanical alterations provide highways for invading carcinoma cells either under the guidance of CAFs or following their epithelial to mesenchymal transition (EMT). The increased HA metabolism of a tumor microenvironment instructs carcinoma initiation and dissemination by performing multiple functions. The key effects of HA reviewed here are its role in activating CAFs in pre-malignant and malignant stroma, and facilitating invasion by promoting motility of both CAFs and tumor cells, thus facilitating their invasion. Circulating CAFs (cCAFs) also form heterotypic clusters with circulating tumor cells (CTC), which are considered to be pre-cursors of metastatic colonies. cCAFs are likely required for extravasation of tumors cells and to form a metastatic niche suitable for new tumor colony growth. Therapeutic interventions designed to target both HA and CAFs in order to limit tumor spread and increase response to current therapies are discussed.
登录
查看更多内容
影响因子：
4
作者：
Folgueira MA;Maistro S;Katayama ML;Roela RA;Mundim FG;Nanogaki S;de Bock GH;Brentani MM
通讯作者：
Brentani MM
影响因子：
10.5
作者：
Brichkina A;Bertero T;Loh HM;Nguyen NT;Emelyanov A;Rigade S;Ilie M;Hofman P;Gaggioli C;Bulavin DV
通讯作者：
Bulavin DV
影响因子：
3.7
作者：
Bharadwaj, Alamelu G.;Goodrich, Nathaniel P.;McAtee, Caitlin O.;Haferbier, Katie;Oakley, Gregory G.;Wahl, James K., III;Simpson, Melanie A.
通讯作者：
Simpson, Melanie A.
影响因子：
3.2
作者：
Brentnall TA
通讯作者：
Brentnall TA
DOI：
10.1056/nejmoa1614814
发表时间：
2017-05-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Anglesio MS;Papadopoulos N;Ayhan A;Nazeran TM;Noë M;Horlings HM;Lum A;Jones S;Senz J;Seckin T;Ho J;Wu RC;Lac V;Ogawa H;Tessier-Cloutier B;Alhassan R;Wang A;Wang Y;Cohen JD;Wong F;Hasanovic A;Orr N;Zhang M;Popoli M;McMahon W;Wood LD;Mattox A;Allaire C;Segars J;Williams C;Tomasetti C;Boyd N;Kinzler KW;Gilks CB;Diaz L;Wang TL;Vogelstein B;Yong PJ;Huntsman DG;Shih IM
通讯作者：
Shih IM