Clinical Relevance of estrogen reactivity in the breast cancer microenvironment
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PROVIDER: PRJNA818635 | ENA |
REPOSITORIES: ENA
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Project description:Estrogen signals play an important role in the phenotype of estrogen receptor positive breast cancer. However, comprehensive analyses of the effect of estrogen signals on the tumor microenvironment and sur-vival in large cohorts of primary breast cancer patients have been lacking. We aimed to test the hypothesis that estrogen reactivity affects gene expression and immune cell infiltration profiles in the tumor microenvi-ronment and survival.
2022-04-26 | GSE199135 | GEO
Project description:Estrogen signaling modulates the colon microenvironment during obesity
| PRJNA630214 | ENA
Project description:Introduction: A gene expression signature indicative of active wound responses is common to more than 90% of non-neoplastic tissues adjacent to breast cancer, but these tissues also show substantial heterogeneity, suggesting different microenvironmental subtypes. Genomic variation in the extratumoral microenvironment has received limited study. Methods: Gene expression analysis from 72 patient-derived samples adjacent to invasive breast cancer or ductal carcinoma in situ was evaluated. Unsupervised clustering identified two distinct gene expression subgroups that differed substantially in expression of genes associated with epithelial-to-mesenchymal transition (EMT). We evaluated the prognostic and biological relevance of this extratumoral EMT-like signature using clinical and experimental approaches. Results: We found that the extratumoral EMT-like signature was not significantly associated with overall survival among all patients [Hazard Ratio (HR) = 1.4, 95% CI 0.6 - 2.8, p=0.337], but there was a strong association with overall survival among estrogen receptor (ER)-positive patients [HR = 2.5, 95% CI 0.9 – 6.7, p=0.062] or hormone-treated patients [HR=2.6, 95% CI 1.0 – 7.0, p=0.045]. In addition, co-culturing of ER-positive MCF-7 cells with cells undergoing EMT increased migration of MCF7 cells in a TGF-β1 dependent manner. Conclusion: Together, these results suggest that the presence of an EMT-like signature in the cancer-adjacent extratumoral microenvironment may influence the aggressiveness of the ER-positive tumors and that ER-positive patients with these extratumoral signatures may require additional treatments or more aggressive surgeries. Reference vs. test sample. 74 test samples (12 breast tumors, 62 normal tissue adjacent to breast tumor) from 72 patients.
2011-12-31 | E-GEOD-31589 | biostudies-arrayexpress
Project description:Epidemiological studies highlight a strong association between obesity and colorectal cancer (CRC). This association appears stronger in men and a role for sex hormones is indicated by epidemiological studies. Especially estrogen is protective against CRC and correlated to several aspects of the metabolic syndrome. Anti-inflammatory and anti-tumorigenic effects of estrogen in colon have been demonstrated to act via estrogen receptor beta (ERβ). This led us to hypothesize that estrogenic signaling, through both systemic and local effects might modulate the colon microenvironment during HFD-induced obesity. In order to test our hypothesis mice were fed a control diet or a high fat diet (HFD) for 3 weeks and treated with different estrogenic ligands. In the present study, we demonstrate that there are sex-differences in the response to HFD-induced obesity and in the colon transcriptome. Both sexes develop obesity with an impaired circadian rhythm but the male metabolic profile is more sensitive to HFD and increased the colon epithelial cell proliferation. Females were resistant to impaired glucose metabolism, but HFD-feeding increased the infiltration of macrophages. Estrogen signaling in males, via ERα, presented anti-obesogenic effects. However, systemic and/or local activation of both ERα and ERβ restored the circadian rhythm in the males. In females, systemic activation of ERα restored the circadian rhythm, however, systemic and/or local activation of ERβ down-regulated the expression of macrophage markers. These results suggest that estrogen signaling through systemic and/or local activation of ERβ can regulate the colon microenvironment during HFD-induced obesity.
2020-10-07 | GSE149811 | GEO
Project description:Understanding how differentiation, microenvironment, and hormonal milieu influence human breast cell susceptibility to malignant transformation will require the use of physiologically relevant in vitro systems. We developed a 3D culture model that enables the propagation of normal estrogen receptor alpha (ER)+ cells. The purpose of this experiment was to assess ER functionality and compare estrogen-induced transcripts among samples and systems.
2018-06-15 | GSE115112 | GEO
Project description:Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment. The relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors, is complex. Low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, but very high levels are immune suppressive. Breast tumor incidence is increased by obesity and age, which interact to influence inflammatory cell populations in normal breast tissue. The molecular impact of these factors on tumor initiation and growth is not well-understood. We modeled the difference in gene expression between 195 breast adenocarcinomas and 195 matched adjacent normal breast tissue samples, using age, body mass index (BMI), and tumor subtype as covariates. Age and BMI were independently associated with inflammation in normal tissue but not tumors. Older patients with ER-positive disease had tumors with higher levels of Estrogen Receptor (ER) signaling compared to adjacent normal tissue and had lower relative levels of tumor macrophage expression. We developed a novel statistic to quantify the rewiring of gene co-expression networks and demonstrate that in ER-positive tumors basal gene networks are rewired even though their expression levels of these genes are not significantly different from those in adjacent normal tissue. Patient age influences the molecular profile of ER-positive breast tumors. Our data support an immunosuppressive effect of estrogen signaling in the breast tumor microenvironment, suggesting this effect contributes to the greater presence of prognostic and therapeutically relevant immune cells in ER-negative tumors. 137 total samples: 43 mammaplastic reduction, 47 breast adenocarcinoma, 47 paired adjacent normal breast tissue
2016-07-01 | E-GEOD-70905 | biostudies-arrayexpress
Project description:Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment. The relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors, is complex. Low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, but very high levels are immune suppressive. Breast tumor incidence is increased by obesity and age, which interact to influence inflammatory cell populations in normal breast tissue. The molecular impact of these factors on tumor initiation and growth is not well-understood. We modeled the difference in gene expression between 195 breast adenocarcinomas and 195 matched adjacent normal breast tissue samples, using age, body mass index (BMI), and tumor subtype as covariates. Age and BMI were independently associated with inflammation in normal tissue but not tumors. Older patients with ER-positive disease had tumors with higher levels of Estrogen Receptor (ER) signaling compared to adjacent normal tissue and had lower relative levels of tumor macrophage expression. We developed a novel statistic to quantify the rewiring of gene co-expression networks and demonstrate that in ER-positive tumors basal gene networks are rewired even though their expression levels of these genes are not significantly different from those in adjacent normal tissue. Patient age influences the molecular profile of ER-positive breast tumors. Our data support an immunosuppressive effect of estrogen signaling in the breast tumor microenvironment, suggesting this effect contributes to the greater presence of prognostic and therapeutically relevant immune cells in ER-negative tumors. 296 total samples: 148 breast adenocarcinoma, 148 paired adjacent normal breast tissue
2016-07-01 | E-GEOD-70947 | biostudies-arrayexpress
Project description:Introduction: A gene expression signature indicative of active wound responses is common to more than 90% of non-neoplastic tissues adjacent to breast cancer, but these tissues also show substantial heterogeneity, suggesting different microenvironmental subtypes. Genomic variation in the extratumoral microenvironment has received limited study. Methods: Gene expression analysis from 72 patient-derived samples adjacent to invasive breast cancer or ductal carcinoma in situ was evaluated. Unsupervised clustering identified two distinct gene expression subgroups that differed substantially in expression of genes associated with epithelial-to-mesenchymal transition (EMT). We evaluated the prognostic and biological relevance of this extratumoral EMT-like signature using clinical and experimental approaches. Results: We found that the extratumoral EMT-like signature was not significantly associated with overall survival among all patients [Hazard Ratio (HR) = 1.4, 95% CI 0.6 - 2.8, p=0.337], but there was a strong association with overall survival among estrogen receptor (ER)-positive patients [HR = 2.5, 95% CI 0.9 – 6.7, p=0.062] or hormone-treated patients [HR=2.6, 95% CI 1.0 – 7.0, p=0.045]. In addition, co-culturing of ER-positive MCF-7 cells with cells undergoing EMT increased migration of MCF7 cells in a TGF-β1 dependent manner. Conclusion: Together, these results suggest that the presence of an EMT-like signature in the cancer-adjacent extratumoral microenvironment may influence the aggressiveness of the ER-positive tumors and that ER-positive patients with these extratumoral signatures may require additional treatments or more aggressive surgeries.
2011-12-31 | GSE31589 | GEO
Project description:The lymphatic system is a common avenue for the spread of breast cancer cells and dissemination through it occurs at least as frequently as hematogenous metastasis. Approximately 75% of primary breast cancers are estrogen receptor (ER) positive and the majority of these maintain receptor expression as lymph node (LN) metastases. However, it is unknown if ER function is equivalent in cancer cells growing in the breast and in the LNs. We have developed a model to assess estrogen responsiveness in ER(+) breast tumors and LN metastases. Fluorescent ER(+) MCF-7 tumors were grown in ovariectomized nude mice supplemented with estradiol. Once axillary LN metastasis arose, estradiol was withdrawn (EWD), for 1 or 4 weeks, or continued, to assess estradiol responsiveness. On EWD, proliferation rates fell similarly in tumors and LN metastases. However, estradiol-dependent ER down-regulation and progesterone receptor induction were deficient in LN metastases, indicating that ER-dependent transcriptional function was altered in the LN. Cancer cells from estradiol-treated and EWD primary tumors and matched LN metastases were isolated by laser capture microdissection. Global gene expression profiling identified transcripts that were regulated by the tissue microenvironment, by hormones, or by both. Interestingly, numerous genes that were estradiol regulated in tumors lost estradiol sensitivity or were regulated in the opposite direction by estradiol in LN metastases. We propose that the LN microenvironment alters estradiol signaling and may contribute to local antiestrogen resistance. Experiment Overall Design: 10 samples, including 3 each of estrogen and estrogen withdrawn axillary lymph nodes and 2 each of estrogen and estrogen withdrawn primary mammary gland tumors.
2008-06-11 | E-GEOD-11317 | biostudies-arrayexpress
Project description:Chronic inflammation promotes breast tumor growth and invasion by accelerating angiogenesis and tissue remodeling in the tumor microenvironment. The relationship between inflammation and estrogen, which drives the growth of 70 percent of breast tumors, is complex. Low levels of estrogen exposure stimulate macrophages and other inflammatory cell populations, but very high levels are immune suppressive. Breast tumor incidence is increased by obesity and age, which interact to influence inflammatory cell populations in normal breast tissue. The molecular impact of these factors on tumor initiation and growth is not well-understood. We modeled the difference in gene expression between 195 breast adenocarcinomas and 195 matched adjacent normal breast tissue samples, using age, body mass index (BMI), and tumor subtype as covariates. Age and BMI were independently associated with inflammation in normal tissue but not tumors. Older patients with ER-positive disease had tumors with higher levels of Estrogen Receptor (ER) signaling compared to adjacent normal tissue and had lower relative levels of tumor macrophage expression. We developed a novel statistic to quantify the rewiring of gene co-expression networks and demonstrate that in ER-positive tumors basal gene networks are rewired even though their expression levels of these genes are not significantly different from those in adjacent normal tissue. Patient age influences the molecular profile of ER-positive breast tumors. Our data support an immunosuppressive effect of estrogen signaling in the breast tumor microenvironment, suggesting this effect contributes to the greater presence of prognostic and therapeutically relevant immune cells in ER-negative tumors.
2016-07-01 | GSE70905 | GEO