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.

中文翻译：

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YKL-39 作为癌症抗血管生成治疗的潜在新靶点。


YKL-39 属于进化上保守的含 Glyco_18 蛋白家族，由几丁质酶和几丁质酶样蛋白组成。几丁质酶样蛋白（CLP）是分泌型凝集素，由于其催化结构域中的氨基酸取代而缺乏水解活性，并且结合了细胞因子和生长因子的功能。在包括癌症在内的各种病理学中产生 CLP 的主要细胞来源之一是巨噬细胞。募集到肿瘤部位并由肿瘤细胞编程的单核细胞分化为肿瘤相关巨噬细胞（TAM），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 是由乳腺癌中的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并刺激血管生成。化疗是在手术干预前减少肿瘤大小和侵袭性的常见策略，但导致肿瘤复发的化疗耐药性是一个常见的临床问题，对癌症患者的生存至关重要。越来越多的证据表明 TAM 是化学耐药性的重要调节剂。我们最近发现，YKL-39 表达水平升高表明接受新辅助化疗的患者转移过程的效率。我们建议YKL-39作为抗血管生成治疗的新靶点，可与新辅助化疗相结合，以减少乳腺癌患者的化疗耐药性并抑制转移。