Oxalate induces breast cancer

Abstract

BackgroundMicrocalcifications 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.MethodsWe 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.ResultsTo 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.ConclusionsWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1747-2) contains supplementary material, which is available to authorized users.

Maize Oxalyl-CoA Decarboxylase1 Degrades Oxalate and Affects the Seed Metabolome and Nutritional Quality

“…Moreover, ingestion of free oxalate or metal oxalate crystals may cause serious diseases. For example, oxalate can induce breast cancer and Ca oxalate crystals are associated with kidney stone composition and urinary metabolic disturbances (Taylor and Curhan, 2007;Gil et al, 2013;Lorenz et al, 2013;Kirejczyk et al, 2014;Castellaro et al, 2015). Therefore, the content of oxalate in food plants must be strictly regulated and a better understanding of the mechanisms underlying oxalate biosynthesis and degradation is of theoretical and practical importance for genetic improvement of crop plants.…”

Dystrophic Large Calcification in Breast Cancer

“…Breast cancer typically associates calcification [1]. Up to 50 % of all non-palpable breast cancers are detected through microcalcifications on mammography, whereas up to 93 % of cases of ductal carcinoma in situ (DCIS) present microcalcifications [1].…”

“…Breast cancer typically associates calcification [1]. Up to 50 % of all non-palpable breast cancers are detected through microcalcifications on mammography, whereas up to 93 % of cases of ductal carcinoma in situ (DCIS) present microcalcifications [1]. Breast cancers presenting with microcalcifications are more often associated with lymph node invasion and HER-2 positivity [1,2], which results in a poorer prognosis.…”

“…Breast calcifications can be classified at the molecular level in two different types: type I calcifications composed of calcium oxalate (CaOx), and type II calcifications composed of calcium phosphate, mainly hydroxyapatite (CaP) [1]. CaOx crystals have been associated both with carcinomas (invasive as well in situ lesions) and with benign cystic breast lesions [1]. Oxalate is an organic dicarboxylate presenting as free oxalic acid, as soluble salts such as sodium or potassium oxalates, or as insoluble salts such as calcium oxalate crystals.…”

Microcalcification on mammography: approaches to interpretation and biopsy

“…Calcium oxalate cannot be metabolized by mammalian cells and there is emerging evidence that exposure to high levels of oxalate may affect epithelial cells by triggering cellular and genetic changes. 1 Calcium phosphate, usually in the form of calcium hydroxyapatite (similar to the form of calcium laid down in bone during skeletal growth 2 ), is more easily recognized in histopathology as it stains purple with haematoxylin and eosin. It is more commonly associated with malignant lesions than calcium oxalate.…”