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The Role of BRCA1/2-Mutated Tumor Microenvironment in Breast Cancer

BRCA1/2突變的腫瘤微環(huán)境在乳腺癌中 的作用

The link between BRCA1/2 mutations and high susceptibility to breast cancer development has been well-established for years. However, the potential impact of BRCA1/2 mutations on the individual cell populations within the unique tumor microenvironment and their relation to breast cancer has been understudied. This review aims to provide significant insights into up-to-date knowledge about the role of BRCA1/2-mutated tumor microenvironment and possible mechanisms by which it interacts with and promotes breast cancer development and progression. Uncovering and exposing these mechanisms of the aberrant microenvironment might provide more effective strategies for treatment of germline mutation-carrying breast cancer patients.

BRCA1/2突變與乳腺癌發(fā)展的高易感性 之間的聯(lián)系已被證實(shí)多年。然而，BRCA1/2突變對獨(dú)特腫瘤微環(huán)境中單個細(xì)胞群的潛在影響及其與乳腺癌的關(guān)系尚未得到充分研究。本綜述旨在提供有關(guān)BRCA1/2突變腫瘤微環(huán)境作用的最新知識及其與乳腺癌發(fā)生和進(jìn)展相互作用并促進(jìn)其發(fā)生和進(jìn)展的可能機(jī)制的重要見解。揭示和揭示異常微環(huán)境的這些機(jī)制可能為治療攜帶種系突變的乳腺癌患者提供更有效的策略。

三角細(xì)胞搖瓶

Taking into account the factors of high incidence rate, prevalence and mortality, breast cancer represents a crucial social and economic burden. Most cases of breast cancer develop as a consequence of somatic mutations accumulating in mammary epithelial cells throughout lifetime and approximately 5–10% can be ascribed to monogenic predispositions. Even though the role of genetic predispositions in breast cancer is well described in the context of genetics, very little is known about the role of the microenvironment carrying the same aberrant cells impaired by the germline mutation in the breast cancer development and progression. Based on the clinical observations, carcinomas carrying mutations in hereditary tumor-suppressor genes involved in maintaining genome integrity such as BRCA1/2 have worse prognosis and aggressive behavior. One of the mechanisms clarifying the aggressive nature of BRCA-associated tumors implies alterations within the surrounding adipose tissue itself. The objective of this review is to look at the role of BRCA1/2 mutations in the context of breast tumor microenvironment and plausible mechanisms by which it contributes to the aggressive behavior of the tumor cells

考慮到高發(fā)病率、患病率和死亡率等因素，乳腺癌是一項(xiàng)至關(guān)重要的社會和經(jīng)濟(jì)負(fù)擔(dān)。大多數(shù)乳腺癌病例是由于體細(xì)胞突變在整個生命周期中在乳腺上皮細(xì)胞中積累的結(jié)果，大約 5-10% 可歸因于單基因易感性。盡管遺傳易感性在乳腺癌中的作用在遺傳學(xué)背景下得到了很好的描述，但對于攜帶受種系突變損害的相同異常細(xì)胞的微環(huán)境在乳腺癌發(fā)展和進(jìn)展中的作用知之甚少。根據(jù)臨床觀察，攜帶參與維持基因組完整性的遺傳性腫瘤抑制基因突變的癌癥，如BRCA1/2預(yù)后較差，具有攻擊性行為。闡明BRCA相關(guān)腫瘤侵襲性的機(jī)制之一意味著周圍脂肪組織本身的改變。本綜述的目的是研究BRCA1/2突變在乳腺腫瘤微環(huán)境中的作用，以及它促成腫瘤細(xì)胞攻擊行為的可能機(jī)制。 

PETG血清培養(yǎng)基瓶

The tumor microenvironment, as another dimension of tumor complexity, has been acknowledged as an important hallmark of cancer more than decade ago. In many aspects it dictates and impacts the tumor behavior and treatment response. However, how the various cells residing in the TME of germline BRCA1/BRCA2-deficient breast tumors that are equally impaired by the same germline mutation contribute to the pathogenesis of the hereditary breast cancer has not been consistently addressed. Results of several experimental and preclinical studies unequivocally point to the need to study not only the tumor epithelial cells, but also the wider concept of TME in which the BRCA genes exert their functions. This review aimed to provide significant insights into up-to-date knowledge about the role of BRCA1/2-mutated tumor microenvironment and possible mechanisms by which it interacts with and promotes breast cancer development and progression. Uncovering and exposing these mechanisms of the aberrant microenvironment might provide more effective strategies for treatment of germline mutation-carrying breast cancer patients.

高效搖瓶

腫瘤微環(huán)境作為腫瘤復(fù)雜性的另一個維度，在十多年前已被公認(rèn)為癌癥的重要標(biāo)志。在許多方面，它決定并影響腫瘤行為和治療反應(yīng)。然而，存在于生殖系BRCA1/BRCA2缺陷型乳腺腫瘤的 TME 中的各種細(xì)胞，它們同樣受到相同的生殖系突變的損害，如何導(dǎo)致遺傳性乳腺癌的發(fā)病機(jī)制尚未得到一致解決。幾項(xiàng)實(shí)驗(yàn)和臨床前研究的結(jié)果明確指出，不僅需要研究腫瘤上皮細(xì)胞，還需要研究更廣泛的 TME 概念，其中BRCA基因發(fā)揮其功能。本綜述旨在提供有關(guān)BRCA1/2突變腫瘤微環(huán)境作用的最新知識及其與乳腺癌發(fā)生和進(jìn)展相互作用并促進(jìn)其發(fā)生和進(jìn)展的可能機(jī)制的重要見解。揭示和揭示異常微環(huán)境的這些機(jī)制可能為治療攜帶種系突變的乳腺癌患者提供更有效的策略。

關(guān)鍵詞： 乳腺癌,腫瘤微環(huán)境,BRCA1/2突變,基質(zhì)細(xì)胞,上皮間質(zhì)轉(zhuǎn)化,血管生成, breast cancer,tumor microenvironment,BRCA1/2?mutations,stromal cells,epithelial-to-mesenchymal transition, angiogenesis

來源：MDPI https://www.mdpi.com/2072-6694/13/3/575/htm