Distinct Expression Patterns of Fibrillar Collagen Types I, III, and V in Association with Mammary Gland Remodeling during Pregnancy, Lactation and Weaning

Tsutsui, Shiori; Wakasa, Haruka; Tsugami, Yusaku; Suzuki, Takahiro; Nishimura, Takanori; Kobayashi, Ken

doi:10.1007/s10911-020-09457-0

Cited by 10 publications

(6 citation statements)

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“…In rodents, the postpartum biology of weaning-induced mammary gland involution has been shown to promote breast cancer dissemination from the primary site through a microenvironmental, tumor cell extrinsic mechanism. Involution returns the lactation-competent gland to a quiescent, prepregnancy-like state via a wound-healing process that includes inflammation and active immune suppression, fibroblast activation, deposition of wound-like fibrillar collagens, and lymphangiogenesis . These stromal attributes are causally linked to metastasis in rodent models of PPBC .…”

Section: Discussionmentioning

confidence: 99%

Young-Onset Breast Cancer Outcomes by Time Since Recent Childbirth in Utah

et al. 2022

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ImportanceBreast cancer diagnosed within 5 to 10 years after childbirth, called postpartum breast cancer (PPBC), is associated with increased risk for metastasis and death. Whether a postpartum diagnosis is an independent risk factor or a surrogate marker of cancer features associated with poor outcomes remains understudied.ObjectiveTo determine whether diagnostic temporal proximity to childbirth is associated with features of breast cancer associated with poor outcomes, including tumor stage, estrogen receptor (ER) status, and risk for distant metastasis and breast cancer–specific mortality, using a population database from the state of Utah.Design, Setting, and ParticipantsThis population-based cohort study using the Utah Population Database (UPDB) included individuals with stage I to III breast cancer diagnosed at age 45 years or younger between 1996 and 2017, followed-up until February 2020. Participant data were analyzed from November 2019 to August 2022.ExposureThe primary exposures were no prior childbirth or time between most recent childbirth and breast cancer diagnosis. Patients were grouped by diagnoses within less than 5 years, 5 to less than 10 years, or 10 years or more since recent childbirth.Main Outcomes and MeasuresThe 2 primary outcomes were distant metastasis–free survival and breast cancer–specific death. Cox proportional hazard models were used to investigate associations between exposures and outcomes adjusting for diagnosis year, patient age, tumor stage, and estrogen receptor (ER) status.ResultsOf 2970 individuals with breast cancer diagnosed at age 45 years or younger (mean [SD] age, 39.3 [5.0] years; 12 Black individuals [0.4%], 2679 White individuals [90.2%]), breast cancer diagnosis within 5 years of recent childbirth was independently associated with approximately 1.5-fold elevated risk for metastasis (hazard ratio [HR], 1.5; 95% CI, 1.2-2.0) and breast cancer–specific death (HR, 1.5; 95% CI, 1.1-2.1) compared with nulliparous individuals. For cancers classically considered to have tumor features associated with good outcomes (ie, stage I or II and ER-positive), a postpartum diagnosis was a dominant feature associated with increased risk for metastasis and death (eg, for individuals with ER-positive disease diagnosed within &lt;5 years of childbirth: age-adjusted metastasis HR, 1.5; 95% CI, 1.1-2.1; P = .01; age-adjusted death HR, 1.5; 95% CI, 1.0-2.1; P = .04) compared with nulliparous individuals. Furthermore, liver metastases were specifically increased in the group with diagnosis within 5 years postpartum and with positive ER expression (38 of 83 patients [45.8%]) compared with the nulliparous (28 of 77 patients [36.4%]), although the difference was not statistically significant. Overall, these data implicate parity-associated breast and liver biology in the observed poor outcomes of PPBC.Conclusions and RelevanceIn this cohort study of individuals with breast cancer diagnosed at age 45 years or younger, a postpartum breast cancer diagnosis was a risk factor associated with poor outcomes. Irrespective of ER status, clinical consideration of time between most recent childbirth and breast cancer diagnosis could increase accuracy of prognosis in patients with young-onset breast cancer.

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Section: Discussionmentioning

confidence: 99%

Young-Onset Breast Cancer Outcomes by Time Since Recent Childbirth in Utah

et al. 2022

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“…Numerous mRNA targets of let-7g-5p associated with lactation traits include hormone signaling ( PRLR , INSR ) [ 43 , 44 , 45 ], extracellular matrix ( COL1A1-2, COL3A1, COL4A1-3 and A6, COL5A2, COL14A1, COL27A1 ) [ 46 ], zinc transport ( SLC30A4 ) [ 47 ], H + transport ( ATP6V1G1, ATP6V1C1 ) [ 48 ], and calcium transport ( ATP2A2, ATP2B4 ) [ 49 ], further implicating it as a regulatory hub for maintaining milk supply. Importantly, our study confirmed that PRLR expression was indeed regulated by let-7g-5p in MECs, providing direct evidence that let-7g-5p is a critical regulator of lactation.…”

Section: Discussionmentioning

confidence: 99%

Human Milk-Derived Levels of let-7g-5p May Serve as a Diagnostic and Prognostic Marker of Low Milk Supply in Breastfeeding Women

et al. 2023

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Low milk supply (LMS) is associated with early breastfeeding cessation; however, the biological underpinnings in the mammary gland are not understood. MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally downregulate gene expression, and we hypothesized the profile of miRNAs secreted into milk reflects lactation performance. Longitudinal changes in milk miRNAs were measured using RNAseq in women with LMS (n = 47) and adequate milk supply (AMS; n = 123). Relationships between milk miRNAs, milk supply, breastfeeding outcomes, and infant weight gain were assessed, and interactions between milk miRNAs, maternal diet, smoking status, and BMI were determined. Women with LMS had lower milk volume (p = 0.003), were more likely to have ceased breast feeding by 24 wks (p = 0.0003) and had infants with a lower mean weight-for-length z-score (p = 0.013). Milk production was significantly associated with milk levels of miR-16-5p (R = −0.14, adj p = 0.044), miR-22-3p (R = 0.13, adj p = 0.044), and let-7g-5p (R = 0.12, adj p = 0.046). Early milk levels of let-7g-5p were significantly higher in mothers with LMS (adj p = 0.0025), displayed an interaction between lactation stage and milk supply (p < 0.001), and were negatively related to fruit intake (p = 0.015). Putative targets of let-7g-5p include genes important to hormone signaling, RNA regulation, ion transport, and the extracellular matrix, and down-regulation of two targets (PRLR and IGF2BP1/IMP1) was confirmed in mammary cells overexpressing let-7g-5p in vitro. Our data provide evidence that milk-derived miRNAs reflect lactation performance in women and warrant further investigation to assess their utility for predicting LMS risk and early breastfeeding cessation.

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“…A study evaluating various miRNAs expressed in dairy heifers and dairy cows showed that COL1A2 is one of the genes associated with the cytoskeleton and extracellular matrix and is associated with mammary gland functional activity (Wicik et al 2016 ). In a study by Tsutsui et al ( 2020 ) On the pattern of expression of different types of fibril collagen in different periods of pregnancy, lactation, and after breastfeeding, it was stated that type I collagen produces a suitable fibrillar structure during pregnancy, while this structure after pregnancy broken. during calving temporary dense fibrillar network is formed by type III fibrillar collagen.…”

Section: Discussionmentioning

confidence: 99%

“…during calving temporary dense fibrillar network is formed by type III fibrillar collagen. it has been generally reported that these collagens are involved in the structural reconstruction of the mammary glands and their function (Tsutsui et al 2020 ). In a study, miRNA and mRNA Expression Profiles in Mammary Glands of Holstein Cows infected by S. aureus were investigated and COL1A2 was one of the most significant DEGs involved in many pathways (Wang et al 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Potential Pathways Associated with Mastitis Induced by E. coli

et al. 2022

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Mastitis is one of the most important diseases of dairy cattle. It is an infectious disease leading to an inflammatory reaction in the cow's mammary gland. Escherichia coli is one of the common bacteria which induce mastitis in cows. The aim of this study was to identify key genes and potential pathways associated with mastitis induced by E. coli in dairy cattle using bioinformatics analysis. The gene expression profile of ten samples including five adjacent tissues from a quarter infected with Escherichia coli and five tissues from a healthy quarter of dairy cattle was assessed using GEO2R. Gene ontology and pathway analysis were performed using bioinformatics tools. A total of 156 differentially expressed genes were detected which 95 genes were upregulated and 61 genes were downregulated in adjacent tissue of quarter infected compared with healthy tissue. Cellular oxidant detoxification and oxidation–reduction process were the most significant biological process terms in gene ontology analysis. The most important pathways of DEGs were the biosynthesis of amino acids, p53 signaling pathway, and Metabolic pathways. Three important modules were identified and their path enrichment analysis was performed. There are 10 core genes, among which SOD2, COL1A2, COL3A1, POSTN, ALDH18A1 , and CBS may be the main genes associated with mastitis, which can be considered as candidate genes in the prevention and carly diagnosis program of mastitis.

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Distinct Expression Patterns of Fibrillar Collagen Types I, III, and V in Association with Mammary Gland Remodeling during Pregnancy, Lactation and Weaning

Cited by 10 publications

References 58 publications

Young-Onset Breast Cancer Outcomes by Time Since Recent Childbirth in Utah

Young-Onset Breast Cancer Outcomes by Time Since Recent Childbirth in Utah

Human Milk-Derived Levels of let-7g-5p May Serve as a Diagnostic and Prognostic Marker of Low Milk Supply in Breastfeeding Women

Identification of Key Genes and Potential Pathways Associated with Mastitis Induced by E. coli

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