Medical Faculty Mannheim, Institute of Transfusion Medicine and Immunology, University of Heidelberg, Mannheim, Germany.
German Red Cross Blood Service Baden-Württemberg-Hessen, Mannheim, Germany.
Front Immunol. 2020 Jan 22;10:2930. doi: 10.3389/fimmu.2019.02930. eCollection 2019.
YKL-39 belongs to the evolutionarily conserved family of Glyco_18-containing proteins composed of chitinases and chitinase-like proteins. Chitinase-like proteins (CLPs) are secreted lectins that lack hydrolytic activity due to the amino acid substitutions in their catalytic domain and combine the functions of cytokines and growth factors. One of the major cellular sources that produce CLPs in various pathologies, including cancer, are macrophages. Monocytes recruited to the tumor site and programmed by tumor cells differentiate into tumor-associated macrophages (TAMs), which are the primary source of pro-angiogenic factors. Tumor angiogenesis is a crucial process for supplying rapidly growing tumors with essential nutrients and oxygen. We recently determined that YKL-39 is produced by tumor-associated macrophages in breast cancer. YKL-39 acts as a strong chemotactic factor for monocytes and stimulates angiogenesis. Chemotherapy is a common strategy to reduce tumor size and aggressiveness before surgical intervention, but chemoresistance, resulting in the relapse of tumors, is a common clinical problem that is critical for survival in cancer patients. Accumulating evidence indicates that TAMs are essential regulators of chemoresistance. We have recently found that elevated levels of YKL-39 expression are indicative of the efficiency of the metastatic process in patients who undergo neoadjuvant chemotherapy. We suggest YKL-39 as a new target for anti-angiogenic therapy that can be combined with neoadjuvant chemotherapy to reduce chemoresistance and inhibit metastasis in breast cancer patients.
YKL-39 属于糖基化 18 蛋白家族，该家族由几丁质酶和几丁质酶样蛋白组成，在进化上是保守的。几丁质酶样蛋白（CLP）是分泌的凝集素，由于其催化结构域中的氨基酸取代，缺乏水解活性，并结合细胞因子和生长因子的功能。在包括癌症在内的各种病理中，产生 CLP 的主要细胞来源是巨噬细胞。单核细胞被募集到肿瘤部位，并被肿瘤细胞编程分化为肿瘤相关巨噬细胞（TAMs），这是促血管生成因子的主要来源。肿瘤血管生成是为快速生长的肿瘤提供必需营养和氧气的关键过程。我们最近确定 YKL-39 是乳腺癌中肿瘤相关巨噬细胞产生的。YKL-39 作为单核细胞的强趋化因子，刺激血管生成。化疗是一种常见的策略，用于在手术干预前缩小肿瘤大小并降低侵袭性，但化疗耐药性导致肿瘤复发，这是癌症患者生存的关键临床问题。越来越多的证据表明 TAMs 是化疗耐药性的重要调节剂。我们最近发现，在接受新辅助化疗的患者中，YKL-39 表达水平升高与转移过程的效率相关。我们提出 YKL-39 作为一种新的抗血管生成治疗靶点，与新辅助化疗联合使用，可以降低乳腺癌患者的化疗耐药性并抑制转移。
