Mito
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- Dec 10, 2016
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Abstract
Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MGDAs) promote growth of breast cancer cells that express monocarboxylate transporter 2 (MCT2) both in vitroand in vivo. We show that β-hydroxybutyrate is secreted by MGDAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, β-hydroxybutyrate is sufficient to promote tumorigenesis of a mouse xenograft model of MCT2-expressing breast cancer cells. Mechanistically we observe that upon co-culturing with MGDAs or treatment with β-hydroxybutyrate, breast cancer cells expressing MCT2 increase the global histone H3K9 acetylation and upregulate several tumour-promoting genes. These results suggest that adipocytes promote malignancy of MCT2-expressing breast cancer via β-hydroxybutyrate potentially by inducing the epigenetic upregulation of tumour-promoting genes.
In addition to adipokines, an elevated level of oestrogen was thought to be the major factor for ERα-positive breast cancer risk in postmenopausal women27
Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate : Nature Communications
Ray has said that β-hydroxybutyrate isn't really a keytone and tends toward the cancer metabolism.
"...the keytone body ratio and what they talk about usually as keytones actually one of them isn't a keytone at all and the ratio of these so called keytone bodies is acetoacetate, β-hydroxybutyrate and the hydroxy is a hydroxy or an alcohol not a keytone and cancer physiology is high in the hydroxy's the reduced form and low in the actual keytones and what you want is the actual high keytone body ratio keeping the alcohols low because that goes with the NADH/NAD ratio being in cancer the NADH reduced form is higher..."
Adipocytes are the most abundant stromal partners in breast tissue. However, the crosstalk between breast cancer cells and adipocytes has been given less attention compared to cancer-associated fibroblasts. Here we find, through systematic screening, that primary mammary gland-derived adipocytes (MGDAs) promote growth of breast cancer cells that express monocarboxylate transporter 2 (MCT2) both in vitroand in vivo. We show that β-hydroxybutyrate is secreted by MGDAs and is required to enhance breast cancer cells malignancy in vitro. Consistently, β-hydroxybutyrate is sufficient to promote tumorigenesis of a mouse xenograft model of MCT2-expressing breast cancer cells. Mechanistically we observe that upon co-culturing with MGDAs or treatment with β-hydroxybutyrate, breast cancer cells expressing MCT2 increase the global histone H3K9 acetylation and upregulate several tumour-promoting genes. These results suggest that adipocytes promote malignancy of MCT2-expressing breast cancer via β-hydroxybutyrate potentially by inducing the epigenetic upregulation of tumour-promoting genes.
In addition to adipokines, an elevated level of oestrogen was thought to be the major factor for ERα-positive breast cancer risk in postmenopausal women27
Adipocytes promote malignant growth of breast tumours with monocarboxylate transporter 2 expression via β-hydroxybutyrate : Nature Communications
Ray has said that β-hydroxybutyrate isn't really a keytone and tends toward the cancer metabolism.
"...the keytone body ratio and what they talk about usually as keytones actually one of them isn't a keytone at all and the ratio of these so called keytone bodies is acetoacetate, β-hydroxybutyrate and the hydroxy is a hydroxy or an alcohol not a keytone and cancer physiology is high in the hydroxy's the reduced form and low in the actual keytones and what you want is the actual high keytone body ratio keeping the alcohols low because that goes with the NADH/NAD ratio being in cancer the NADH reduced form is higher..."
