Microenvironment and endocrine resistance in breast cancer: Friend or foe?

Recouvreux, Sol; Sampayo, Rocío; Bessone, María Inés Díaz; Simian, Marina

doi:10.5306/wjco.v6.i6.207

Cited by 8 publications

(7 citation statements)

References 38 publications

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“…However, a high percentage of patients develop resistance, and up to one third of them have cancer recurrence within 15 years [106]. Previous studies suggest that hormone therapy could modulate TME which then induces treatment resistance.…”

Section: Hormonal Therapymentioning

confidence: 99%

Complex interplay between tumor microenvironment and cancer therapy

Shen

Kang

2018

Front. Med.

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Tumor microenvironment (TME) is comprised of cellular and non-cellular components that exist within and around the tumor mass. The TME is highly dynamic and its importance in different stages of cancer progression has been well recognized. A growing body of evidence suggests that TME also plays pivotal roles in cancer treatment responses. TME is significantly remodeled upon cancer therapies, and such change either enhances the responses or induces drug resistance. Given the importance of TME in tumor progression and therapy resistance, strategies that remodel TME to improve therapeutic responses are under developing. In this review, we provide an overview of the essential components in TME and the remodeling of TME in response to anti-cancer treatments. We also summarize the strategies that aim to enhance therapeutic efficacy by modulating TME.

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Section: Hormonal Therapymentioning

confidence: 99%

Complex interplay between tumor microenvironment and cancer therapy

Shen

Kang

2018

Front. Med.

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“…Interestingly, in an in vitro model, EGF and FGF have been shown to drive breast cancer cell resistance to letrozole via activation of the PI3K signaling pathway [ 55 ]. Other studies have shown that the cytokine IL-1β activates ER transcriptional activity and modulates response to 4-OH-tamoxifen, rendering it an agonist instead of an antagonist (reviewed in [ 59 ]). Other studies also suggest that stromal and immune cells within the tumor microenvironment may play a role in promoting endocrine resistance (reviewed in [ 59 ]).…”

Section: Discussionmentioning

confidence: 99%

“…Other studies have shown that the cytokine IL-1β activates ER transcriptional activity and modulates response to 4-OH-tamoxifen, rendering it an agonist instead of an antagonist (reviewed in [ 59 ]). Other studies also suggest that stromal and immune cells within the tumor microenvironment may play a role in promoting endocrine resistance (reviewed in [ 59 ]). And finally, Bernoulli et al have recently described a mouse model in which estrogen supplementation is required to support the growth of orthotopic ER+ MCF-7 primary tumors, but not ER+ MCF-7 lesions in the skeleton [ 60 ].…”

Section: Discussionmentioning

confidence: 99%

Local estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells

et al. 2017

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BackgroundApproximately 70% of all breast cancers express the estrogen receptor, and are regulated by estrogen. While the ovaries are the primary source of estrogen in premenopausal women, most breast cancer is diagnosed following menopause, when systemic levels of this hormone decline. Estrogen production from androgen precursors is catalyzed by the aromatase enzyme. Although aromatase expression and local estrogen production in breast adipose tissue have been implicated in the development of primary breast cancer, the source of estrogen involved in the regulation of estrogen receptor-positive (ER+) metastatic breast cancer progression is less clear.MethodsBone is the most common distant site of breast cancer metastasis, particularly for ER+ breast cancers. We employed a co-culture model using trabecular bone tissues obtained from total hip replacement (THR) surgery specimens to study ER+ and estrogen receptor-negative (ER-) breast cancer cells within the human bone microenvironment. Luciferase-expressing ER+ (MCF-7, T-47D, ZR-75) and ER- (SK-BR-3, MDA-MB-231, MCF-10A) breast cancer cells were cultured directly on bone tissue fragments or in bone tissue-conditioned media, and monitored over time with bioluminescence imaging (BLI). Bone tissue-conditioned media were generated in the presence vs. absence of aromatase inhibitors, and testosterone. Bone tissue fragments were analyzed for aromatase expression by immunohistochemistry.ResultsER+ breast cancer cells were preferentially sustained in co-cultures with bone tissues and bone tissue-conditioned media relative to ER- cells. Bone fragments analyzed by immunohistochemistry revealed expression of the aromatase enzyme. Bone tissue-conditioned media generated in the presence of testosterone had increased estrogen levels and heightened capacity to stimulate ER+ breast cancer cell proliferation. Pretreatment of cultured bone tissues with aromatase inhibitors, which inhibited estrogen production, reduced the capacity of conditioned media to stimulate ER+ cell proliferation.ConclusionsThese results suggest that a local estrogen signaling axis regulates ER+ breast cancer cell viability and proliferation within the bone metastatic niche, and that aromatase inhibitors modulate this axis. Although endocrine therapies are highly effective in the treatment of ER+ breast cancer, resistance to these treatments reduces their efficacy. Characterization of estrogen signaling networks within the bone microenvironment will identify new strategies for combating metastatic progression and endocrine resistance.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0910-x) contains supplementary material, which is available to authorized users.

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“…Inflammation is a major contributor to hormone resistance [200,201], which is in part through stimulation of BCSCs. In this regard, gene expression profiling of MCF7-derived BCSCs shows an upregulation of inflammatory cytokines (like IL8) [202].…”

Section: Mechanisms Underlying Bcsc Enrichment Following the Develmentioning

confidence: 99%

The Central Contributions of Breast Cancer Stem Cells in Developing Resistance to Endocrine Therapy in Estrogen Receptor (ER)-Positive Breast Cancer

Rodriguez

Ramkairsingh

Lin

et al. 2019

Cancers

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Breast cancer stem cells (BCSC) play critical roles in the acquisition of resistance to endocrine therapy in estrogen receptor (ER)-positive (ER + ve) breast cancer (BC). The resistance results from complex alterations involving ER, growth factor receptors, NOTCH, Wnt/β-catenin, hedgehog, YAP/TAZ, and the tumor microenvironment. These mechanisms are likely converged on regulating BCSCs, which then drive the development of endocrine therapy resistance. In this regard, hormone therapies enrich BCSCs in ER + ve BCs under both pre-clinical and clinical settings along with upregulation of the core components of “stemness” transcriptional factors including SOX2, NANOG, and OCT4. SOX2 initiates a set of reactions involving SOX9, Wnt, FXY3D, and Src tyrosine kinase; these reactions stimulate BCSCs and contribute to endocrine resistance. The central contributions of BCSCs to endocrine resistance regulated by complex mechanisms offer a unified strategy to counter the resistance. ER + ve BCs constitute approximately 75% of BCs to which hormone therapy is the major therapeutic approach. Likewise, resistance to endocrine therapy remains the major challenge in the management of patients with ER + ve BC. In this review we will discuss evidence supporting a central role of BCSCs in developing endocrine resistance and outline the strategy of targeting BCSCs to reduce hormone therapy resistance.

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Microenvironment and endocrine resistance in breast cancer: Friend or foe?

Cited by 8 publications

References 38 publications

Complex interplay between tumor microenvironment and cancer therapy

Complex interplay between tumor microenvironment and cancer therapy

Local estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells

The Central Contributions of Breast Cancer Stem Cells in Developing Resistance to Endocrine Therapy in Estrogen Receptor (ER)-Positive Breast Cancer

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