School of Biomedical Sciences, University of Queensland, St Lucia, Queensland, Australia.
Cancer Sci. 2010 Feb;101(2):369-73. doi: 10.1111/j.1349-7006.2009.01399.x. Epub 2009 Oct 12.
Sulfate plays an important role in maintaining normal structure and function of tissues, and its content is decreased in certain cancers including lung carcinoma. In this study, we investigated tumor growth in a mouse model of hyposulfatemia (Nas1(-/-)) and compared it to wild-type (Nas1(+/+)) mice. Lung epithelial tumor cells (TC-1 cell line) were injected subcutaneously into male Nas1(-/-) and Nas1(+/+) mice on a mixed 129Sv and C57BL/6 genetic background. Tumor sections were stained with anti-glycosaminoglycan antibodies to assess the distribution of proteoglycans and Gomori's trichrome to detect collagen. After 14 days, tumor weights were markedly increased (by approximately 12-fold) in Nas1(-/-) mice when compared with Nas1(+/+) mice. Histological analyses of tumors revealed increased (by approximately 2.4-fold) vessel content, as well as markedly reduced collagen and immunoreactivity against glycosaminoglycan structural epitopes in the tumors from Nas1(-/-) mice. No significant differences were found for the growth of cultured TC-1 cells supplemented with Nas1(-/-) or Nas1(+/+) serum, as determined by (3)H-thymidine incorporation, implying that the cell culture conditions may not reflect the in vivo situation of enhanced tumor growth. This study has revealed increased tumor growth and an altered extracellular tumor matrix in hyposulfatemic Nas1(-/-) mice. These findings highlight the importance of blood sulfate levels as a possible modulator of tumor growth, and could lead to future cancer studies in humans with altered sulfate homeostasis.
硫酸盐在维持组织的正常结构和功能方面起着重要作用，其在某些癌症中含量降低，包括肺癌。在这项研究中，我们研究了低硫酸盐血症（Nas1(-/-)）小鼠模型中的肿瘤生长，并将其与野生型（Nas1(+/+)）小鼠进行了比较。将肺上皮肿瘤细胞（TC-1 细胞系）皮下注射到混合 129Sv 和 C57BL/6 遗传背景的雄性 Nas1(-/-)和 Nas1(+/+)小鼠中。用抗糖胺聚糖抗体对肿瘤切片进行染色，以评估蛋白聚糖的分布，并使用 Gomori 三色法检测胶原。14 天后，与 Nas1(+/+)小鼠相比，Nas1(-/-)小鼠的肿瘤重量显著增加（约增加 12 倍）。肿瘤的组织学分析显示，Nas1(-/-)小鼠的肿瘤血管含量增加（约增加 2.4 倍），以及胶原和糖胺聚糖结构表位的免疫反应性明显降低。通过（3）H-胸腺嘧啶掺入法确定，用 Nas1(-/-)或 Nas1(+/+)血清补充培养的 TC-1 细胞的生长没有差异，这表明细胞培养条件可能无法反映体内增强肿瘤生长的情况。这项研究揭示了低硫酸盐血症 Nas1(-/-)小鼠中肿瘤生长增加和细胞外肿瘤基质改变。这些发现强调了血液硫酸盐水平作为肿瘤生长的可能调节剂的重要性，并可能导致未来对硫酸盐动态平衡改变的人类癌症研究。
