Lactate stimulates fibroblast expression of hyaluronan and CD44: The Warburg effect revisited
Lactate stimulates fibroblast expression of hyaluronan and CD44: The Warburg effect revisited
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DOI：
10.1006/excr.2002.5508
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发表时间：
2002-05-15
影响因子：
3.7
通讯作者：
Fromby, B
中科院分区：
文献类型：
--
作者：
Stern, R;Shuster, S;Fromby, B
Hybryonan是细胞外基质的一种高分子量糖胺聚糖，在快速组织生长和修复过程中非常突出。它刺激细胞运动和水合组织，提供一个环境，促进细胞运动。透明质酸水平的显著提高也发生在人类癌症周围的基质中，从而提供了促进癌细胞扩散的环境。恶性肿瘤产生乳酸的能力，即使在足够的氧气存在下，被称为瓦尔堡效应。伤口愈合早期，随着血液和氧气供应减少，乳酸盐水平增加，基质透明质酸也增加，这表明存在因果关系。类似地，瘤周基质成纤维细胞透明质酸可能是对癌细胞乳酸的反应。为了测试这一点，在乳酸盐存在下培养成纤维细胞。随着乳酸的增加，观察到更高水平的透明质酸，以及透明质酸的主要受体CD44表达水平。肿瘤细胞利用厌氧代谢和产生乳酸的能力，即使在存在足够的氧气供应的情况下，可能是用于募集宿主成纤维细胞以存款透明质酸和表达CD 44的机制之一，从而参与癌症侵袭和转移的过程。(C)2002 Elsevier Science（美国）。
Hyaluronan, a high-molecular-weight glycosaminoglycan of the extracellular matrix, is prominent during rapid tissue growth and repair. It stimulates cell motility and hydrates tissue, providing an environment that facilitates cell movement. Markedly enhanced levels of hyaluronan also occur in the stroma surrounding human cancers, thus providing an environment that promotes spread of cancer cells. The ability of malignant tumors to generate lactate, even in the presence of adequate oxygen, is known as the Warburg effect. Early in wound healing as blood and oxygen supply decrease, lactate levels increase, as does stromal hyaluronan, suggesting a cause-and-effect relationship. Similarly, peritumor stromal fibroblast hyaluronan may be a response to cancer cell lactate. To test this, fibroblasts were cultured in the presence of lactate. With increasing lactate, higher levels of hyaluronan were observed, as were levels of CD44 expression, the predominant receptor for hyaluronan. The ability of tumor cells to utilize anaerobic metabolism and to generate lactate, even in the presence of adequate supplies of oxygen, may be one of the mechanisms used to recruit host fibroblasts to deposit hyaluronan and to express CD44, thereby participating in the process of cancer invasion and metastasis. (C) 2002 Elsevier Science (USA).