Adipocytes in Breast Cancer, the Thick and the Thin

Rybińska, Ilona; Agresti, Roberto; Trapani, A; Tagliabue, Elda; Triulzi, Tiziana

doi:10.3390/cells9030560

Cited by 62 publications

(75 citation statements)

References 158 publications

(196 reference statements)

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“…We have found that intratumoral adipocyte-high breast cancer enriched for the inflammation, metastasis, and cancer stemness related gene sets, which is in agreement with the previous reports [25,[49][50][51][52]. This was more significant with the ER+/HER2-subtype compared with TNBC.…”

Section: Discussionsupporting

confidence: 92%

“…Cancer-associated adipocytes are known to promote tumor growth, invasion, and migration of breast cancer cells in vitro [25]. To this end, we hypothesized that tumors that were high in intratumoral adipocytes would be associated with the advanced American Joint Commission on Cancer (AJCC) clinical cancer staging in the TCGA cohort.…”

Section: Intratumoral Adipocyte-high Tumors Were Not Associated Withmentioning

confidence: 99%

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Intratumoral Adipocyte-High Breast Cancer Enrich for Metastatic and Inflammation-Related Pathways but Associated with Less Cancer Cell Proliferation

Tokumaru

Oshi

Katsuta

et al. 2020

IJMS

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Cancer-associated adipocytes are known to cause inflammation, leading to cancer progression and metastasis. The clinicopathological and transcriptomic data from 2256 patients with breast cancer were obtained based on three cohorts: The Cancer Genome Atlas (TCGA), GSE25066, and a study by Yau et al. For the current study, we defined the adipocyte, which is calculated by utilizing a computational algorithm, xCell, as “intratumoral adipocyte”. These intratumoral adipocytes appropriately reflected mature adipocytes in a bulk tumor. The amount of intratumoral adipocytes demonstrated no relationship with survival. Intratumoral adipocyte-high tumors significantly enriched for metastasis and inflammation-related gene sets and are associated with a favorable tumor immune microenvironment, especially in the ER+/HER2- subtype. On the other hand, intratumoral adipocyte-low tumors significantly enriched for cell cycle and cell proliferation-related gene sets. Correspondingly, intratumoral adipocyte-low tumors are associated with advanced pathological grades and inversely correlated with MKI67 expression. In conclusion, a high amount of intratumoral adipocytes in breast cancer was associated with inflammation, metastatic pathways, cancer stemness, and favorable tumor immune microenvironment. However, a low amount of adipocytes was associated with a highly proliferative tumor in ER-positive breast cancer. This cancer biology may explain the reason why patient survival did not differ by the amount of adipocytes.

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Section: Discussionsupporting

confidence: 92%

Section: Intratumoral Adipocyte-high Tumors Were Not Associated Withmentioning

confidence: 99%

Intratumoral Adipocyte-High Breast Cancer Enrich for Metastatic and Inflammation-Related Pathways but Associated with Less Cancer Cell Proliferation

Tokumaru

Oshi

Katsuta

et al. 2020

IJMS

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“…A recent review by Rybinska et al, 2020, showed an increase in TNFα, IL-6, IL-1β, CCL2, adiponectin and collagen and a decrease in leptin in BC causing anorexia leading to cachexia. Furthermore, BC mediated cachexia is also associated with a decrease in adipogenesis transcription factors PPARγ, c/EBPα, GLUT4 and SREBP-1, and an increase in HSL, an enzyme responsible for lipolytic activity in cachexia [235].…”

Section: Cachexiamentioning

confidence: 99%

The Importance of Breast Adipose Tissue in Breast Cancer

Kothari

Diorio

Durocher

2020

IJMS

112

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Adipose tissue is a complex endocrine organ, with a role in obesity and cancer. Adipose tissue is generally linked to excessive body fat, and it is well known that the female breast is rich in adipose tissue. Hence, one can wonder: what is the role of adipose tissue in the breast and why is it required? Adipose tissue as an organ consists of adipocytes, an extracellular matrix (ECM) and immune cells, with a significant role in the dynamics of breast changes throughout the life span of a female breast from puberty, pregnancy, lactation and involution. In this review, we will discuss the importance of breast adipose tissue in breast development and its involvement in breast changes happening during pregnancy, lactation and involution. We will focus on understanding the biology of breast adipose tissue, with an overview on its involvement in the various steps of breast cancer development and progression. The interaction between the breast adipose tissue surrounding cancer cells and vice-versa modifies the tumor microenvironment in favor of cancer. Understanding this mutual interaction and the role of breast adipose tissue in the tumor microenvironment could potentially raise the possibility of overcoming breast adipose tissue mediated resistance to therapies and finding novel candidates to target breast cancer.

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“…The tumor-provoked hypermetabolism in CC leads to a state of energy imbalance that cannot be recovered through nutritional supplementation (Kir and Spiegelman, 2016;Vaitkus and Celi, 2017). According to morphologic modifications, decreased lipid content and a proinflammatory phenotype, cachectic adipocytes are similar to TAAs (Rybinska et al, 2020). As recently demonstrated, the downregulation of adipogenic and lipogenic genes is affected early in AT, resulting in lipolysis and AT remodeling during CC (Batista et al, 2013;Sun et al, 2020).…”

Section: Tumor-induced Adipose Tissue Remodelingmentioning

confidence: 97%

Adipogenesis in Different Body Depots and Tumor Development

Trivanović¹,

Petrinović

Djordjević

et al. 2020

Front. Cell Dev. Biol.

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Adipose tissue (AT) forms depots at different anatomical locations throughout the body, being in subcutaneous and visceral regions, as well as the bone marrow. These ATs differ in the adipocyte functional profile, their insulin sensitivity, adipokines' production, lipolysis, and response to pathologic conditions. Despite the recent advances in lineage tracing, which have demonstrated that individual adipose depots are composed of adipocytes derived from distinct progenitor populations, the cellular and molecular dissection of the adipose clonogenic stem cell niche is still a great challenge. Additional complexity in AT regulation is associated with tumor-induced changes that affect adipocyte phenotype. As an integrative unit of cell differentiation, AT microenvironment regulates various phenotype outcomes of differentiating adipogenic lineages, which consequently may contribute to the neoplastic phenotype manifestations. Particularly interesting is the capacity of AT to impose and support the aberrant potency of stem cells that accompanies tumor development. In this review, we summarize the current findings on the communication between adipocytes and their progenitors with tumor cells, pointing out to the coexistence of healthy and neoplastic stem cell niches developed during tumor evolution. We also discuss tumor-induced adaptations in mature adipocytes and the involvement of alternative differentiation programs.

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Adipocytes in Breast Cancer, the Thick and the Thin

Cited by 62 publications

References 158 publications

Intratumoral Adipocyte-High Breast Cancer Enrich for Metastatic and Inflammation-Related Pathways but Associated with Less Cancer Cell Proliferation

Intratumoral Adipocyte-High Breast Cancer Enrich for Metastatic and Inflammation-Related Pathways but Associated with Less Cancer Cell Proliferation

The Importance of Breast Adipose Tissue in Breast Cancer

Adipogenesis in Different Body Depots and Tumor Development

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