Cathepsin C is a tissue-specific regulator of squamous carcinogenesis.
Cathepsin C is a tissue-specific regulator of squamous carcinogenesis.
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DOI：
10.1101/gad.224899.113
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发表时间：
2013-10-01
影响因子：
10.5
通讯作者：
Coussens LM
中科院分区：
文献类型：
--
作者：
Ruffell B;Affara NI;Cottone L;Junankar S;Johansson M;DeNardo DG;Korets L;Reinheckel T;Sloane BF;Bogyo M;Coussens LM
丝氨酸和半胱氨酸组织蛋白酶（Cts）蛋白酶参与肿瘤进展。CtsB在乳腺癌发生过程中起重要作用。Ruffell等人发现鳞状细胞癌的发展与CtsB无关。CtsC在乳腺癌发生过程中是不需要的，但在鳞状细胞癌发生过程中是必需的。真皮/基质成纤维细胞和骨髓源性细胞表达升高水平的酶活性CtsC，其调节肿瘤皮肤中浸润免疫细胞的复杂性、血管生成血管系统的发育和鳞状细胞癌生长。这些发现表明，组织特异性可以定义功能意义。丝氨酸和半胱氨酸组织蛋白酶（Cts）蛋白酶是一类重要的细胞内和细胞周酶，其介导肿瘤发展的多个方面。这些的象征是CtsB，据报道在胰岛和乳腺癌发生过程中发挥重要的功能作用。另一方面，CtsC虽然在胰岛癌变过程中上调，但在介导该器官的肿瘤进展中缺乏功能意义。鉴于CtsB和CtsC的蛋白表达和酶活性在许多肿瘤中增加，我们试图了解组织特异性如何影响其功能意义。因此，尽管其他人已经报道了CtsB调节乳腺癌的转移，但我们发现鳞状细胞癌的发展独立于CtsB。与这些研究结果相反，我们的研究发现CtsC在乳腺癌发生过程中没有显着的作用，但显示鳞状细胞癌的功能依赖于CtsC。在这种情况下，真皮/基质成纤维细胞和骨髓来源的细胞表达水平增加的酶活性CtsC，调节肿瘤皮肤中浸润免疫细胞的复杂性，血管生成血管系统的发展，和明显的鳞状细胞癌生长。这些研究突出了组织/微环境背景对实体瘤发展的重要贡献，并表明组织特异性定义了半胱氨酸蛋白酶家族这两个成员的功能意义。
Serine and cysteine cathepsin (Cts) proteases are involved in tumor progression. CtsB plays a significant role during mammary carcinogenesis. Ruffell et al. find that squamous carcinomas develop independently of CtsB. CtsC is not required during mammary carcinogenesis but is necessary for squamous carcinogenesis. Dermal/stromal fibroblasts and bone marrow-derived cells express elevated levels of enzymatically active CtsC that regulate the complexity of infiltrating immune cells in neoplastic skin, development of angiogenic vasculature, and squamous cell carcinoma growth. These findings indicate that tissue specificity can define functional significance. Serine and cysteine cathepsin (Cts) proteases are an important class of intracellular and pericellular enzymes mediating multiple aspects of tumor development. Emblematic of these is CtsB, reported to play functionally significant roles during pancreatic islet and mammary carcinogenesis. CtsC, on the other hand, while up-regulated during pancreatic islet carcinogenesis, lacks functional significance in mediating neoplastic progression in that organ. Given that protein expression and enzymatic activity of both CtsB and CtsC are increased in numerous tumors, we sought to understand how tissue specificity might factor into their functional significance. Thus, whereas others have reported that CtsB regulates metastasis of mammary carcinomas, we found that development of squamous carcinomas occurs independently of CtsB. In contrast to these findings, our studies found no significant role for CtsC during mammary carcinogenesis but revealed squamous carcinogenesis to be functionally dependent on CtsC. In this context, dermal/stromal fibroblasts and bone marrow-derived cells expressed increased levels of enzymatically active CtsC that regulated the complexity of infiltrating immune cells in neoplastic skin, development of angiogenic vasculature, and overt squamous cell carcinoma growth. These studies highlight the important contribution of tissue/microenvironment context to solid tumor development and indicate that tissue specificity defines functional significance for these two members of the cysteine protease family.
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影响因子：
10.5
作者：
Coussens, LM;Raymond, WW;Hanahan, D
通讯作者：
Hanahan, D
影响因子：
4.3
作者：
Gocheva, Vasilena;Joyce, Johanna A.
通讯作者：
Joyce, Johanna A.
影响因子：
4.1
作者：
BUCK, MR;KARUSTIS, DG;SLOANE, BF
通讯作者：
SLOANE, BF
影响因子：
50.3
作者：
DeNardo DG;Barreto JB;Andreu P;Vasquez L;Tawfik D;Kolhatkar N;Coussens LM
通讯作者：
Coussens LM
影响因子：
15.9
作者：
Adkison, AM;Raptis, SZ;Pham, CTN
通讯作者：
Pham, CTN