Interleukin-34 Enhances the Tumor Promoting Function of Colorectal Cancer-Associated Fibroblasts.
Interleukin-34 Enhances the Tumor Promoting Function of Colorectal Cancer-Associated Fibroblasts.
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白介素34增强结直肠癌相关成纤维细胞的促癌功能
DOI：
10.3390/cancers12123537
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发表时间：
2020-11-27
期刊：
影响因子：
5.2
通讯作者：
Monteleone G
中科院分区：
文献类型：
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作者：
Franzè E;Di Grazia A;Sica GS;Biancone L;Laudisi F;Monteleone G
在结直肠癌（CRC）中，癌症相关成纤维细胞（CAF）通过合成靶向肿瘤细胞的各种分子促进肿瘤生长和进展。在这里，我们证明了IL-34，一种在CRC组织中高度表达的细胞因子，以旁分泌和自分泌的方式调节CAFs的功能。具体地，IL-34诱导正常成纤维细胞（NF）获得类似于CAF的细胞表型，而CAF中的IL-34敲低降低了它们的致瘤特性和增殖。此外，IL-34刺激NF产生netrin-1和b-FGF-两种增强CRC细胞生长和迁移的因子。总之，我们的数据支持IL-34参与CRC。结直肠癌（CRC）的间质区室以存在大量成纤维细胞（称为癌症相关成纤维细胞（CAF））为标志，其通过合成靶向肿瘤细胞的各种分子促进CRC生长和进展。白细胞介素（IL）-34，一种由CRC细胞过度产生的细胞因子，刺激CRC细胞生长。由于IL-34也调节炎性成纤维细胞的功能，我们假设它可以调节结直肠CAF的促肿瘤功能。通过免疫染色和实时PCR，我们最初表明，IL-34是由CAFs高度产生的，在较小程度上由从CRC患者的非肿瘤结肠粘膜分离的正常成纤维细胞产生。CAFs和正常成纤维细胞表达IL-34的功能性受体。IL-34诱导正常成纤维细胞表达α-SMA、波形蛋白和成纤维细胞活化蛋白，并促进成纤维细胞生长，从而产生类似于CAF的细胞表型。一致地，用反义寡核苷酸（AS）敲低CAFs中的IL-34降低了这些标志物的表达并抑制了细胞增殖。CRC细胞与IL-34 AS处理的CAF上清液的共培养导致较少的癌细胞增殖和迁移。在已知促进CRC细胞生长/迁移的CAF衍生分子中，只有netrin-1和碱性成纤维细胞生长因子被IL-34诱导。数据表明IL-34在控制结肠直肠CAF功能中的作用。
In colorectal cancer (CRC), cancer-associated fibroblasts (CAFs) promote tumor growth and progression through the synthesis of various molecules targeting the neoplastic cells. Here, we demonstrate that IL-34, a cytokine highly expressed in CRC tissue, regulates the function of CAFs in a paracrine and autocrine manner. Specifically, IL-34 induces normal fibroblasts (NFs) to acquire a cellular phenotype resembling that of CAFs, while IL-34 knockdown in CAFs reduces their tumorigenic properties and proliferation. Moreover, IL-34 stimulates NFs to produce netrin-1 and b-FGF—two factors that enhance CRC cell growth and migration. Altogether, our data support the involvement of IL-34 in CRC. The stromal compartment of colorectal cancer (CRC) is marked by the presence of large numbers of fibroblasts, termed cancer-associated fibroblasts (CAFs), which promote CRC growth and progression through the synthesis of various molecules targeting the neoplastic cells. Interleukin (IL)-34, a cytokine over-produced by CRC cells, stimulates CRC cell growth. Since IL-34 also regulates the function of inflammatory fibroblasts, we hypothesized that it could regulate the tumor promoting function of colorectal CAFs. By immunostaining and real-time PCR, we initially showed that IL-34 was highly produced by CAFs and to lesser extent by normal fibroblasts isolated from non-tumoral colonic mucosa of CRC patients. CAFs and normal fibroblasts expressed the functional receptors of IL-34. IL-34 induced normal fibroblasts to express α-SMA, vimentin and fibroblast activation protein and enhanced fibroblast growth, thus generating a cellular phenotype resembling that of CAFs. Consistently, knockdown of IL-34 in CAFs with an antisense oligonucleotide (AS) decreased expression of such markers and inhibited cell proliferation. Co-culture of CRC cells with IL-34 AS-treated CAFs supernatants resulted in less cancer cell proliferation and migration. Among CAF-derived molecules known to promote CRC cell growth/migration, only netrin-1 and basic-fibroblast growth factor were induced by IL-34. Data suggest a role for IL-34 in the control of colorectal CAF function.
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影响因子：
--
作者：
Franzè E;Dinallo V;Rizzo A;Di Giovangiulio M;Bevivino G;Stolfi C;Caprioli F;Colantoni A;Ortenzi A;Grazia AD;Sica G;Sileri PP;Rossi P;Monteleone G
通讯作者：
Monteleone G
DOI：
10.1158/1541-7786.mcr-12-0307
发表时间：
2012-11
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Karagiannis GS;Poutahidis T;Erdman SE;Kirsch R;Riddell RH;Diamandis EP
通讯作者：
Diamandis EP
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
3
作者：
Korc M;Friesel RE
通讯作者：
Friesel RE
影响因子：
6
作者：
Franze, Eleonora;Monteleone, Ivan;Monteleone, Giovanni
通讯作者：
Monteleone, Giovanni