Oxalate induces breast cancer.
Oxalate induces breast cancer.
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DOI：
10.1186/s12885-015-1747-2
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发表时间：
2015-10-22
期刊：
影响因子：
3.8
通讯作者：
Gil GA
中科院分区：
文献类型：
--
作者：
Castellaro AM;Tonda A;Cejas HH;Ferreyra H;Caputto BL;Pucci OA;Gil GA
微钙化可能是乳腺癌的早期和唯一表现。乳腺癌的一个共同特征是乳房X线摄影乳腺微钙化的出现，其可以常规地用于在其初始阶段检测乳腺癌，这是至关重要的，因为早期检测允许应用更保守的治疗以获得更好的患者结果。乳腺微钙化形成的机制在很大程度上仍然是未知的，但乳腺癌表现出微钙化往往与预后较差。我们将毛细管电色谱、组织学和基因表达（qRT-PCR）相结合来分析患者匹配的正常乳腺组织与乳腺肿瘤。通过小鼠接种试验，检测了草酸盐的潜在致癌性。所有数据均进行统计分析。为了研究乳腺肿瘤微环境中草酸盐的生物学意义，我们测量了人乳腺肿瘤组织和邻近非病理性乳腺组织中的草酸盐浓度。我们发现，所有测试的乳腺肿瘤组织都含有比其对应的非病理性乳腺组织更高浓度的脂肪酸盐。此外，已确定草酸盐诱导乳腺细胞增殖并刺激促肿瘤基因c-fos的表达。此外，当将草酸盐注射到雌性小鼠的乳房脂肪垫中时，会产生高度恶性和未分化的肿瘤，但当注射到它们的背部时不会，这表明草酸盐不会在所有类型的组织中诱导癌症形成。此外，当用草酸盐处理时，人肾上皮细胞和小鼠成纤维细胞都不增殖。我们发现，乳腺上皮细胞长期暴露于草酸盐促进乳腺细胞从正常细胞向肿瘤细胞转化，诱导原癌基因c-fos的表达和乳腺癌细胞的增殖。此外，当将草酸盐注射到小鼠的乳房脂肪垫中时，草酸盐具有致癌作用，产生具有乳房纤维肉瘤特征的高度恶性和未分化的肿瘤。由于草酸盐似乎促进了这些差异，如果能够控制草酸盐的产生或其致癌活性，预计乳腺癌肿瘤的发病率将显著降低。本文的在线版本（doi：10.1186/s12885-015-1747-2）包含补充材料，可供授权用户使用。
Microcalcifications can be the early and only presenting sign of breast cancer. One shared characteristic of breast cancer is the appearance of mammographic mammary microcalcifications that can routinely be used to detect breast cancer in its initial stages, which is of key importance due to the possibility that early detection allows the application of more conservative therapies for a better patient outcome. The mechanism by which mammary microcalcifications are formed is still largely unknown but breast cancers presenting microcalcifications are more often associated with a poorer prognosis. We combined Capillary Electrochromatography, histology, and gene expression (qRT-PCR) to analyze patient-matched normal breast tissue vs. breast tumor. Potential carcinogenicity of oxalate was tested by its inoculation into mice. All data were subjected to statistical analysis. To study the biological significance of oxalates within the breast tumor microenvironment, we measured oxalate concentration in both human breast tumor tissues and adjoining non-pathological breast tissues. We found that all tested breast tumor tissues contain a higher concentration of oxalates than their counterpart non-pathological breast tissue. Moreover, it was established that oxalate induces proliferation of breast cells and stimulates the expression of a pro-tumorigenic gene c-fos. Furthermore, oxalate generates highly malignant and undifferentiated tumors when it was injected into the mammary fatpad in female mice, but not when injected into their back, indicating that oxalate does not induce cancer formation in all types of tissues. Moreover, neither human kidney-epithelial cells nor mouse fibroblast cells proliferate when are treated with oxalate. We found that the chronic exposure of breast epithelial cells to oxalate promotes the transformation of breast cells from normal to tumor cells, inducing the expression of a proto-oncogen as c-fos and proliferation in breast cancer cells. Furthermore, oxalate has a carcinogenic effect when injected into the mammary fatpad in mice, generating highly malignant and undifferentiated tumors with the characteristics of fibrosarcomas of the breast. As oxalates seem to promote these differences, it is expected that a significant reduction in the incidence of breast cancer tumors could be reached if it were possible to control oxalate production or its carcinogenic activity. The online version of this article (doi:10.1186/s12885-015-1747-2) contains supplementary material, which is available to authorized users.