The crosstalk within the breast tumor microenvironment in type II diabetes: Implications for cancer disparities.
The crosstalk within the breast tumor microenvironment in type II diabetes: Implications for cancer disparities.
复制标题
DOI：
10.3389/fendo.2022.1044670
复制
发表时间：
2022
影响因子：
5.2
通讯作者：
Denis, Gerald V.
中科院分区：
文献类型：
--
作者：
Ennis, Christina S.;Llevenes, Pablo;Qiu, Yuhan;Dries, Ruben;Denis, Gerald V.
关键词：
肥胖驱动的（2型）糖尿病（T2D）是最常见的代谢紊乱，它会增加乳腺癌所有分子亚型的发病率，并降低绝经后妇女的生存率。尽管存在这种明确的联系，但在肿瘤学的标准治疗实践中，T2D和各种组织的相关功能障碍通常不被考虑，而且被视为许多新兴临床试验的排除标准。这些指南导致T2D和乳腺癌相关的生物学机制未得到充分研究。最近，它已被证明，乳腺肿瘤微环境（TME）的组成和架构，特别是周围的细胞和细胞外结构，决定肿瘤的进展，并直接相关的临床结果。除了上皮癌细胞部分之外，乳腺TME主要由癌症相关的成纤维细胞、脂肪细胞组成，并且通常被免疫细胞浸润。在T2D期间，这些细胞类型之间的信号转导异常，导致功能障碍的乳腺TME，其与附近的癌细胞通信以促进致癌过程、癌症干细胞样细胞形成、促转移行为并增加复发风险。由于这些细胞是非恶性的，尽管它们的信号异常，但关于它们功能的数据从未在DNA突变数据库中捕获，因此我们对公开可用数据集的机制的了解有限。我们认为，与非肥胖、代谢正常患者的乳腺TME相比，肥胖和代谢疾病患者乳腺TME内的异常脂肪细胞和免疫细胞耗竭可能在恶性上皮细胞的扩增群体内引起更大的转录可塑性和细胞异质性。这些挑战与癌症差异设置特别相关，其中在乳腺肿瘤医学实践中看到的患者比例也存在共病肥胖和代谢疾病。在这篇综述中，我们描述了T2D期间乳腺TME的变化，并提出了迫切的分子，细胞和翻译问题，这些问题需要进一步研究，考虑到T2D在全球范围内的日益流行。
Obesity-driven (type 2) diabetes (T2D), the most common metabolic disorder, both increases the incidence of all molecular subtypes of breast cancer and decreases survival in postmenopausal women. Despite this clear link, T2D and the associated dysfunction of diverse tissues is often not considered during the standard of care practices in oncology and, moreover, is treated as exclusion criteria for many emerging clinical trials. These guidelines have caused the biological mechanisms that associate T2D and breast cancer to be understudied. Recently, it has been illustrated that the breast tumor microenvironment (TME) composition and architecture, specifically the surrounding cellular and extracellular structures, dictate tumor progression and are directly relevant for clinical outcomes. In addition to the epithelial cancer cell fraction, the breast TME is predominantly made up of cancer-associated fibroblasts, adipocytes, and is often infiltrated by immune cells. During T2D, signal transduction among these cell types is aberrant, resulting in a dysfunctional breast TME that communicates with nearby cancer cells to promote oncogenic processes, cancer stem-like cell formation, pro-metastatic behavior and increase the risk of recurrence. As these cells are non-malignant, despite their signaling abnormalities, data concerning their function is never captured in DNA mutational databases, thus we have limited insight into mechanism from publicly available datasets. We suggest that abnormal adipocyte and immune cell exhaustion within the breast TME in patients with obesity and metabolic disease may elicit greater transcriptional plasticity and cellular heterogeneity within the expanding population of malignant epithelial cells, compared to the breast TME of a non-obese, metabolically normal patient. These challenges are particularly relevant to cancer disparities settings where the fraction of patients seen within the breast medical oncology practice also present with co-morbid obesity and metabolic disease. Within this review, we characterize the changes to the breast TME during T2D and raise urgent molecular, cellular and translational questions that warrant further study, considering the growing prevalence of T2D worldwide.
登录
查看更多内容
影响因子：
5.9
作者：
Balaban S;Shearer RF;Lee LS;van Geldermalsen M;Schreuder M;Shtein HC;Cairns R;Thomas KC;Fazakerley DJ;Grewal T;Holst J;Saunders DN;Hoy AJ
通讯作者：
Hoy AJ
影响因子：
30.8
作者：
Danenberg E;Bardwell H;Zanotelli VRT;Provenzano E;Chin SF;Rueda OM;Green A;Rakha E;Aparicio S;Ellis IO;Bodenmiller B;Caldas C;Ali HR
通讯作者：
Ali HR
影响因子：
--
作者：
Amoani, Benjamin;Sakyi, Samuel A;Afranie, Bright Oppong
通讯作者：
Afranie, Bright Oppong
影响因子：
3.7
作者：
Alvino CL;Ong SC;McNeil KA;Delaine C;Booker GW;Wallace JC;Forbes BE
通讯作者：
Forbes BE
影响因子：
50.3
作者：
Costa, Ana;Kieffer, Yann;Mechta-Grigoriou, Fatima
通讯作者：
Mechta-Grigoriou, Fatima