Lactate acidosis is often observed in the tumor microenvironment (TME) of solid tumors. This is because glucose breaks down quickly via glycolysis, causing lactate acidity. Lactate is harmful to healthy cells, but is a major oncometabolite for solid cancer cells that do not receive sufficient oxygen. As an oncometabolite, it helps tumor cells perform different functions, which helps solid hypoxic tumor cells spread to other parts of the body. Studies have shown that the acidic TME contains VEGF, Matrix metalloproteinases (MMPs), cathepsins, and transforming growth factor-β (TGF-β), all of which help spread in direct and indirect ways. Although each cytokine is important in its own manner in the TME, TGF-β has received much attention for its role in metastatic transformation. Several studies have shown that lactate acidosis can cause TGF-β expression in solid hypoxic cancers. TGF-β has also been reported to increase the production of fatty acids, making cells more resistant to treatment. TGF-β has also been shown to control the expression of VEGF and MMPs, which helps solid hypoxic tumors become more aggressive by helping them spread and create new blood vessels through an unknown process. The role of TGF-β under physiological conditions has been described previously. In this study, we examined the role of TGF-β, which is induced by lactate acidosis, in the spread of solid hypoxic cancer cells. We also found that TGF-β and lactate work together to boost fatty acid production, which helps angiogenesis and invasiveness.

乳酸酸中毒经常在实体瘤的肿瘤微环境（TME）中观察到。这是因为葡萄糖通过糖酵解快速分解，导致乳酸酸性。乳酸对健康细胞有害，但对于没有获得足够氧气的实体癌细胞来说，它是一种主要的致癌代谢物。作为一种肿瘤代谢物，它可以帮助肿瘤细胞执行不同的功能，从而帮助实体缺氧的肿瘤细胞扩散到身体的其他部位。研究表明，酸性 TME 含有 VEGF、基质金属蛋白酶 (MMP)、组织蛋白酶和转化生长因子-β (TGF-β)，所有这些都有助于以直接和间接方式传播。尽管每种细胞因子在 TME 中都有其重要的作用，但 TGF-β 因其在转移转化中的作用而受到广泛关注。多项研究表明，乳酸酸中毒可导致实体缺氧癌症中 TGF-β 的表达。据报道，TGF-β 还可以增加脂肪酸的产生，使细胞对治疗更具抵抗力。TGF-β 还被证明可以控制 VEGF 和 MMP 的表达，这有助于实体缺氧肿瘤通过未知的过程扩散和产生新血管，从而变得更具侵袭性。之前已经描述了生理条件下 TGF-β 的作用。在这项研究中，我们研究了由乳酸酸中毒诱导的 TGF-β 在固体缺氧癌细胞扩散中的作用。我们还发现 TGF-β 和乳酸共同促进脂肪酸的产生，从而有助于血管生成和侵袭。