Breast tumors of the basal-like, hormone receptor-negative subtype remain an unmet clinical challenge, as there is high rate of recurrence and poor survival in patients following treatment. Coevolution of the malignant mammary epithelium and its underlying stroma instigates cancer-associated fibroblasts (CAFs) to support most, if not all, hallmarks of cancer progression. Here we delineate a previously unappreciated role for CAFs as determinants of the molecular subtype of breast cancer. We identified paracrine crosstalk between cancer cells expressing platelet-derived growth factor (PDGF)-CC and CAFs expressing the cognate receptors in human basal-like mammary carcinomas. Genetic or pharmacological intervention of PDGF-CC activity in mouse models of cancer resulted in conversion of basal-like breast cancers into a hormone receptor-positive state that enhanced sensitivity to endocrine therapy in previously resistant tumors. We conclude that specification of breast cancer to the basal-like subtype is under microenvironmental control and is therapeutically actionable.

中文翻译：

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通过旁分泌血小板衍生生长因子-CC信号诱导的乳腺癌亚型的微环境控制。

基底样、激素受体阴性亚型的乳腺肿瘤仍然是一个未解决的临床挑战，因为治疗后患者的复发率高且生存率低。恶性乳腺上皮及其潜在基质的共同进化促使癌症相关成纤维细胞 (CAF) 支持大多数（如果不是全部）癌症进展的标志。在这里，我们描述了 CAF 作为乳腺癌分子亚型的决定因素以前未被重视的作用。我们确定了表达血小板衍生生长因子 (PDGF)-CC 的癌细胞和表达人类基底样乳腺癌中同源受体的 CAF 之间的旁分泌串扰。对癌症小鼠模型中 PDGF-CC 活性的遗传或药理学干预导致基底样乳腺癌转化为激素受体阳性状态，从而增强了先前耐药肿瘤对内分泌治疗的敏感性。我们得出结论，乳腺癌对基底样亚型的规范处于微环境控制之下，并且在治疗上是可行的。