Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas.
Podoplanin expression in cancer-associated fibroblasts enhances tumor progression of invasive ductal carcinoma of the pancreas.
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DOI：
10.1186/1476-4598-12-168
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发表时间：
2013-12-20
期刊：
影响因子：
37.3
通讯作者：
Oda Y
中科院分区：
文献类型：
--
作者：
Shindo K;Aishima S;Ohuchida K;Fujiwara K;Fujino M;Mizuuchi Y;Hattori M;Mizumoto K;Tanaka M;Oda Y
癌细胞与周围癌症相关成纤维细胞（CAFs）之间的相互作用在癌症进展中起重要作用。胰腺浸润性导管癌（IDC）的特点是纤维结缔组织增生。Podoplanin （PDPN）是一种淋巴管标志物（D2-40），据报道，间质cas表达PDPN是各种类型癌症的预后指标。105例行胰腺切除术的患者通过免疫组化检查评估胰腺IDCs中PDPN的表达。原发性CAFs是在手术获得的胰腺癌组织中建立的。采用定量逆转录聚合酶链反应和流式细胞术检测PDPN在CAFs中的表达。我们根据PDPN的表达对CAFs进行了分类，并采用与胰腺癌细胞系间接共培养的方法分析了PDPN+ CAFs和PDPN - CAFs的功能差异。我们还研究了培养条件对cas中PDPN表达的调节作用。PDPN在间质成纤维细胞中的表达与淋巴管侵袭（P = 0.0461）、血管侵袭（P = 0.0101）、肿瘤大小≥3 cm （P = 0.0038）、组织学分级（P = 0.0344）、国际癌症控制联盟分级T期（P = 0.029）、生存时间较短（P < 0.0001）相关。原代CAFs在体外显示异质PDPN表达。此外，胰腺癌细胞系（PANC-1和SUIT-2）的迁移和侵袭与cas中PDPN的表达（P < 0.01）以及CD10、基质金属蛋白酶（MMP） 2和MMP3的表达相关。在培养的CAFs中，在与癌细胞共培养、不同培养基和添加生长因子等条件下，PDPN阳性随时间变化。表达pdpn的CAFs可促进胰腺IDC的进展，高比例表达pdpn的CAFs是预后不良的独立预测因子。了解肿瘤微环境的调控是开发新的治疗策略的重要一步。
Interactions between cancer cells and surrounding cancer-associated fibroblasts (CAFs) play an important role in cancer progression. Invasive ductal carcinoma (IDC) of the pancreas is characterized by abundant fibrous connective tissue called desmoplasia. Podoplanin (PDPN) is a lymphatic vessel marker (D2-40), and expression of PDPN by stromal CAFs has been reported to be a prognostic indicator in various types of cancer. Expression of PDPN in pancreatic IDCs was assessed by immunohistochemical examination in 105 patients who underwent pancreatic resection. Primary CAFs were established from pancreatic cancer tissue obtained by surgery. Quantitative reverse transcription-polymerase chain reaction and flow cytometric analysis were performed to investigate PDPN expression in CAFs. We sorted CAFs according to PDPN expression, and analyzed the functional differences between PDPN+ CAFs and PDPN– CAFs using indirect co-culture with pancreatic cancer cell lines. We also investigated the culture conditions to regulate PDPN expression in CAFs. PDPN expression in stromal fibroblasts was associated with lymphatic vessel invasion (P = 0.0461), vascular invasion (P = 0.0101), tumor size ≥3 cm (P = 0.0038), histological grade (P = 0.0344), Union for International Cancer Control classification T stage (P = 0.029), and shorter survival time (P < 0.0001). Primary CAFs showed heterogeneous PDPN expression in vitro. Moreover, migration and invasion of pancreatic cancer cell lines (PANC-1 and SUIT-2) were associated with PDPN expression in CAFs (P < 0.01) and expression of CD10, matrix metalloproteinase (MMP) 2, and MMP3. In cultured CAFs, PDPN positivity changed over time under several conditions including co-culture with cancer cells, different culture media, and addition of growth factor. PDPN-expressing CAFs enhance the progression of pancreatic IDC, and a high ratio of PDPN-expressing CAFs is an independent predictor of poor outcome. Understanding the regulation of the tumor microenvironment is an important step towards developing new therapeutic strategies.
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影响因子：
3.5
作者：
Kaneko, Mika Kato;Kato, Yukinari;Osawa, Motoki
通讯作者：
Osawa, Motoki
影响因子：
2.2
作者：
Eguchi, Daiki;Ikenaga, Naoki;Tanaka, Masao
通讯作者：
Tanaka, Masao
影响因子：
29.4
作者：
Froeling, Fieke E. M.;Feig, Christine;Kocher, Hemant M.
通讯作者：
Kocher, Hemant M.
影响因子：
7.5
作者：
Aishima, Shinichi;Nishihara, Yunosuke;Tsuneyoshi, Masazumi
通讯作者：
Tsuneyoshi, Masazumi
DOI：
10.1590/s1807-59322010001200009
发表时间：
2010
期刊：
Clinics (Sao Paulo, Brazil)
影响因子：
--
作者：
Carvalho FM;Zaganelli FL;Almeida BG;Goes JC;Baracat EC;Carvalho JP
通讯作者：
Carvalho JP