Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Dec;17(6):773-785.
doi: 10.1007/s13770-020-00299-9. Epub 2020 Sep 16.

Studying Adipose Tissue in the Breast Tumor Microenvironment In Vitro: Progress and Opportunities

David Mertz  1 , Jason Sentosa  1 , Gary Luker  2 , Shuichi Takayama  3   4
Affiliations
Review

Studying Adipose Tissue in the Breast Tumor Microenvironment In Vitro: Progress and Opportunities

David Mertz et al. Tissue Eng Regen Med. 2020 Dec.

Abstract

Background: The breast cancer microenvironment contains a variety of stromal cells that are widely implicated in worse patient outcomes. While many in vitro models of the breast tumor microenvironment have been published, only a small fraction of these feature adipocytes. Adipocytes are a cell type increasingly recognized to have complex functions in breast cancer.

Methods: In this review, we examine findings from recent examples of in vitro experiments modeling adipocytes within the local breast tumor microenvironment.

Results: Both two-dimensional and three-dimensional models of adipocytes in the breast tumor microenvironment are covered in this review and both have uncovered interesting phenomena related to breast tumor progression.

Conclusion: Certain aspects of breast cancer and associated adipocyte biology: extracellular matrix effects, cell-cell contact, and physiological mass transport can only be examined with a three-dimensional culture platform. Opportunities remain for innovative improvements to be made to in vitro models that further increase what is known about adipocytes during breast cancer progression.

Keywords: 3D culture; Adipocyte; Breast cancer; Microenvironment; Phenotypic assay.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
A The microenvironment around the epithelial breast lobule and duct contains a 3D arrangement of diverse cell types and ECM molecules, creating a unique challenge for tissue engineering in this geometry. B These components have been hypothesized to each possess a role in the progression of primary adenocarcinomas, as early as the transition of ductal carcinoma in situ to invasive ductal carcinoma, through paracrine signaling and matrix remodeling
Fig. 2
Fig. 2
Examples of previously-published 2D adipose/breast tumor cell culture systems. A Transwell migration assay to measure tumor cell migration towards adipocyte-secreted chemoattractants. B Using adipocyteconditioned media for modulation of invasiveness in a scratch-wound assay or modulation of other phenotypic markers of breast tumor cells in 2D culture. C Testing the effects of tumor cell-secreted factors on adipocytes using tumor cell-conditioned media in a 2D adipocyte differentiation assay
Fig. 3
Fig. 3
Previously-published adipose/breast tumor experiments that incorporate elements unique to 3D cultures. A Tumor cells exposed to adipocyte-conditioned media passaged into an agarose-coated surface to test spheroid-forming capability. B Linear invasion assay for breast tumor cells using a transwell platform with layered Matrigel. C Radial invasion assay for a breast tumor spheroid embedded in Matrigel. D Schematic and data from Morgan et al. displaying the cross-section of a tissue-engineered cancerous duct surrounded by adipose stromal cells (AdSCs) from donor patients to demonstrate AdSC modulation of anastrazole sensitivity in an intra-ductal MCF-7 cell population (reproduced with permission from reference 64). The 3D model shows clear distinction between obese and normal weight adipose cell donors compared to data collected from a simple 2D model. Note: The data in red should be correctly recognized as “BMI ≥ 30”. E Schematic and data from Hume et al. displaying how an adipocyte-laden collagen gel stimulates increased interior invasion than a blank control by MDA-MB-231 cells seeded on the upper surface of the gel (reproduced with permission from reference 72). Invaded cells are indicated by red arrowheads in the inset higher magnification view
Fig. 4
Fig. 4
A simple example of how selecting a culture platform may influence adipocyte phenotype. A Example 2D (flat bottom well) and 3D (ultra-low attachment spheroid well) culture platforms for adipose tissue culture. B During differentiation of primary human preadipocytes, the culture platform dictates accumulation rate of the key adipokines adiponectin and leptin in the supernatant. Interestingly, 3D culture severely downregulates production of leptin. All conditions were assayed in triplicate. (*) indicates p < 0.05 when same-day data are compared using a Student’s t test
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Parmar H, Cunha GR. Epithelial-stromal interactions in the mouse and human mammary gland in vivo. Endocr Relat Cancer. 2004;11:437–458. - PubMed
    1. Ward R, Sims AH, Lee A, Lo C, Wynne L, Yusuf H, et al. Monocytes and macrophages, implications for breast cancer migration and stem cell-like activity and treatment. Oncotarget. 2015;6:14687–14699. - PMC - PubMed
    1. Wang YY, Lehuédé C, Laurent V, Dirat B, Dauvillier S, Bochet L, et al. Adipose tissue and breast epithelial cells: a dangerous dynamic duo in breast cancer. Cancer Lett. 2012;324:142–151. - PubMed
    1. Pinilla S, Alt E, Abdul Khalek FJ, Jotzu C, Muehlberg F, Beckmann C, et al. Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion. Cancer Lett. 2009;284:80–85. - PubMed
    1. Zwick RK, Rudolph MC, Shook BA, Holtrup B, Roth E, Lei V, et al. Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation. Nat Commun. 2018;9:3592. - PMC - PubMed

Publication types

LinkOut - more resources