Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation

Zwick, Rachel K.; Rudolph, Michael C.; Shook, Brett A.; Holtrup, Brandon; Roth, Eve; Lei, Vivian; Keymeulen, Alexandra Van; Seewaldt, Victoria; Kwei, Stephanie; Wysolmerski, John J.; Rodeheffer, M.; Horsley, Valerie

doi:10.1038/s41467-018-05911-0

Cited by 89 publications

(65 citation statements)

References 86 publications

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“…Maybe they remain constantly present as smaller, slimmed cells, giving the impression of adipocytes disappearance [16,17]. Considering the above, the post-lactation adipogenesis seems to be a process not involving proliferative events but rather based on lipid trafficking and cytoplasm refilling with components derived from regressing milk-producing cells [18]. Nowadays, we know such particular dialog persists also in pathological conditions, such as cancer.…”

Section: Mammary Adipocytesmentioning

confidence: 99%

Adipocytes in Breast Cancer, the Thick and the Thin

Rybińska

Agresti

Trapani

et al. 2020

Cells

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It is well established that breast cancer development and progression depend not only on tumor-cell intrinsic factors but also on its microenvironment and on the host characteristics. There is growing evidence that adipocytes play a role in breast cancer progression. This is supported by: (i) epidemiological studies reporting the association of obesity with a higher cancer risk and poor prognosis, (ii) recent studies demonstrating the existence of a cross-talk between breast cancer cells and adipocytes locally in the breast that leads to acquisition of an aggressive tumor phenotype, and (iii) evidence showing that cancer cachexia applies also to fat tissue and shares similarities with stromal-carcinoma metabolic synergy. This review summarizes the current knowledge on the epidemiological link between obesity and breast cancer and outlines the results of the tumor-adipocyte crosstalk. We also focus on systemic changes in body fat in patients with cachexia developed in the course of cancer. Moreover, we discuss and compare adipocyte alterations in the three pathological conditions and the mechanisms through which breast cancer progression is induced.

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Section: Mammary Adipocytesmentioning

confidence: 99%

Adipocytes in Breast Cancer, the Thick and the Thin

Rybińska

Agresti

Trapani

et al. 2020

Cells

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“…Adipocyte-derived fibroblasts secrete fibronectin and collagen I and have invasive properties 38,40 . Moreover, during the stromal remodelling stage in involution, there is a re-differentiation of the adipocytes 31,41 . Involution iCAFs, on the other hand, showed pathways linked to a wound-healing process, including inflammation through the complement cascade and coagulation 29,42,43 .…”

Section: Cafs From Pymt/elf5 Mammary Tumours Show Features Of Mimicrymentioning

confidence: 99%

Single cell transcriptomics reveals involution mimicry during the specification of the basal breast cancer subtype

Valdés-Mora

Salomon

Gloss

et al. 2019

Preprint

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Both luminal and basal breast cancer subtypes originate in the mammary luminal progenitor cell compartment. Basal breast cancer is associated with younger age, early relapse, and high mortality rate. Here we used unbiased droplet-based single-cell RNAseq to elucidate the cellular basis of tumour progression during the specification of the basal breast cancer subtype from the luminal progenitor population. Basal-like cancer cells resembled the alveolar lineage that is specified upon pregnancy and showed molecular features indicative of an interaction with the tumour microenvironment (TME) including EMT, hypoxia, lactation and involution. Involution signatures in luminal breast cancer tumours with alveolar lineage features were associated with worse prognosis and features of basal breast cancer. Our highresolution molecular characterisation of the tumour ecosystem also revealed a highly interactive cell-cell network reminiscent of an involution process. This involution mimicry involves malignant education of cancer-associated fibroblasts and myeloid cell recruitment to support tissue remodelling and sustained inflammation. Our study shows how luminal breast cancer acquires a post-lactation developmental program to shift molecular subtype and promote tumour progression, with potential to explain the increased risk of cancer during the post-partum period.

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“…After weaning, when milk production is no longer required, milkproducing epithelial cells are removed, and mammary gland is remodeled into a prepregnancy state. This process is called involution, which includes programmed cell death of the epithelium, ECM remodeling, and redifferentiation of adipocytes (Hughes and Watson, 2012;Macias and Hinck, 2012;Zwick et al, 2018;Jena et al, 2019). By the end of involution, mammary gland is ready for a new cycle of pregnancy-associated growth, lactation, and subsequent involution, which can be repeated throughout the reproductive lifespan.…”

Section: Introductionmentioning

confidence: 99%