Plasma hyaluronidase (Hyal-1) promotes tumor cell cycling
Plasma hyaluronidase (Hyal-1) promotes tumor cell cycling
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DOI：
10.1016/s0304-3835(00)00669-8
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发表时间：
2001-02-10
期刊：
影响因子：
9.7
通讯作者：
Stern, R
中科院分区：
文献类型：
--
作者：
Lin, G;Stern, R
矛盾的是，透明质酸 (HA) 和透明质酸酶都参与恶性转化和癌症进展。鉴于明显的差异，它们的作用机制尚不清楚。在许多恶性肿瘤中，HA 水平与转移行为相关，而透明质酸酶则抑制恶性进展。 Hyal-1 是六种旁系同源透明质酸酶样序列之一的产物，是主要的循环透明质酸酶。 HYAL1 是编码 Hyal-1 的基因，位于染色体 3p21.3 上，该区域包含肿瘤抑制基因。 HYAL1 的缺失通常与肿瘤进展相关，尤其是与烟草相关的癌症。然而，在其他恶性肿瘤中，透明质酸酶起到肿瘤促进剂的作用。睾丸透明质酸酶 (PH-20) 用作化疗的佐剂，被认为可以增强药物渗透性。通过一种未知的机制，透明质酸酶将肿瘤细胞招募回循环库，使这些恶性肿瘤对化疗药物更加敏感。这种矛盾的观察结果可以通过假设在导致恶性转化的多个步骤的不同时间需要HA和透明质酸酶来解决。我们对它们在癌症进展中的作用进行了系统研究。在这里，我们研究了 Hyal-1 表达对细胞周期动力学的影响。使用位于 HYAL1 cDNA 上游的蜕皮激素诱导型启动子构建肿瘤细胞系。荧光激活细胞分选用于监测 Hyal-1 诱导后的细胞周期动力学。观察到细胞周期增强，S 期细胞增加 13.6%，G(1)/G(0) 期细胞减少 9.6%。 (C) 2001 Elsevier Science Ireland Ltd. 保留所有权利。
Paradoxically, both hyaluronan (HA) and hyaluronidase are involved in malignant transformation and cancer progression. Their mechanisms of action, given the apparent disparities, are not understood. In many malignancies, levels of HA correlate with metastatic behavior while hyaluronidases suppress malignant progression. Hyal-1, product of one of six paralogous hyaluronidase-like sequences, is the predominant circulating hyaluronidase. HYAL1, the gene that codes for Hyal-1, is located on chromosome 3p21.3, a region containing a tumor suppressor gene. Loss of HYAL1 often correlates with tumor progression, particularly in tobacco-related cancers. In other malignancies, however, hyaluronidase functions as a tumor promoter. Testicular hyaluronidase (PH-20), used as an adjuvant in chemotherapy, is assumed to enhance drug permeability. By an unknown mechanism, hyaluronidases recruit tumor cells back into the cycling pool, making these malignancies more sensitive to chemotherapeutic drugs. Such contradictory observations might be resolved by assuming that HA and hyaluronidase are required at different times in the multiple steps that lead to malignant transformation. We have undertaken a systematic investigation of their roles in cancer progression. Here, we investigate the effect of Hyal-1 expression on cell cycle kinetics. A tumor cell line was constructed with an ecdysone-inducible promoter located upstream from the cDNA of HYAL1. Fluorescent-activated cell sorting was used to monitor cell cycle kinetics following Hyal-1 induction. Enhanced cell cycling was observed, with a 13.6% increase in S phase and 9.6% decrease in G(1)/G(0) phase cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.