Skip to main content

Advertisement

SpringerLink
Log in

Adipose Stroma Accelerates the Invasion and Escape of Human Breast Cancer Cells from an Engineered Microtumor

  • Original Article
  • Published:
Cellular and Molecular Bioengineering Aims and scope Submit manuscript

Abstract

Introduction

Approximately 20–25% of human breast tumors are found within an adipose, rather than fibrous, stroma. Adipose stroma is associated with an increased risk of lymph node metastasis, but the causal association between adipose stroma and metastatic progression in human breast cancer remains unclear.

Methods

We used micropatterned type I collagen gels to engineer ~3-mm-long microscale human breast tumors within a stroma that contains adipocytes and adipose-derived stem cells (ASCs) (collectively, "adipose cells"). Invasion and escape of human breast cancer cells into an empty 120-μm-diameter lymphatic-like cavity was used to model interstitial invasion and vascular escape in the presence of adipose cell-derived factors for up to 16 days.

Results

We found that adipose cells hasten invasion and escape by 1–2 days and 2–3 days, respectively. These effects were mediated by soluble factors secreted by the adipose cells, and these factors acted directly on tumor cells. Surprisingly, tumor invasion and escape were more strongly induced by ASCs than by adipocytes.

Conclusions

This work reveals that both adipocytes and ASCs accelerate the interstitial invasion and escape of human breast cancer cells, and sheds light on the link between adipose stroma and lymphatic metastasis in human breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Similar content being viewed by others

Abbreviations

ASC:

Adipose-derived stem cell

ECM:

Extracellular matrix

IFP:

Interstitial fluid pressure

References

  1. Acerbi, I., L. Cassereau, I. Dean, Q. Shi, A. Au, C. Park, Y. Y. Chen, J. Liphardt, E. S. Hwang, and V. M. Weaver. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integr. Biol. (Camb.) 7:1120–1134, 2015.

    Article  Google Scholar 

  2. Balaban, S., R. F. Shearer, L. S. Lee, M. van Geldermalsen, M. Schreuder, H. C. Shtein, R. Cairns, K. C. Thomas, D. J. Fazakerley, T. Grewal, J. Holst, D. N. Saunders, and A. J. Hoy. Adipocyte lipolysis links obesity to breast cancer growth: adipocyte-derived fatty acids drive breast cancer cell proliferation and migration. Cancer Metab. 5:1, 2017.

    Article  Google Scholar 

  3. Blanchette-Mackie, E. J., N. K. Dwyer, T. Barber, R. A. Coxey, T. Takeda, C. M. Rondinone, J. L. Theodorakis, A. S. Greenberg, and C. Londos. Perilipin is located on the surface layer of intracellular lipid droplets in adipocytes. J. Lipid Res. 36:1211–1226, 1995.

    Article  Google Scholar 

  4. Bortell, R., T. A. Owen, R. Ignotz, G. S. Stein, and J. L. Stein. TGF-β1 prevents the down-regulation of type I procollagen, fibronectin, and TGF-β1 gene expression associated with 3T3-L1 pre-adipocyte differentiation. J. Cell. Biochem. 54:256–263, 1994.

    Article  Google Scholar 

  5. Butcher, D. T., T. Alliston, and V. M. Weaver. A tense situation: forcing tumour progression. Nat. Rev. Cancer 9:108–122, 2009.

    Article  Google Scholar 

  6. Celis, J. E., J. M. Moreira, T. Cabezón, P. Gromov, E. Friis, F. Rank, and I. Gromova. Identification of extracellular and intracellular signaling components of the mammary adipose tissue and its interstitial fluid in high risk breast cancer patients: toward dissecting the molecular circuitry of epithelial-adipocyte stromal cell interactions. Mol. Cell. Proteomics 4:492–522, 2005.

    Article  Google Scholar 

  7. Chandler, E. M., B. R. Seo, J. P. Califano, R. C. Andresen Eguiluz, J. S. Lee, C. J. Yoon, D. T. Tims, J. X. Wang, L. Cheng, S. Mohanan, M. R. Buckley, I. Cohen, A. Y. Nikitin, R. M. Williams, D. Gourdon, C. A. Reinhart-King and C. Fischbach. Implanted adipose progenitor cells as physicochemical regulators of breast cancer. Proc. Natl. Acad. Sci. USA 109:9786-9791, 2012.

  8. Choi, J., Y. J. Cha, and J. S. Koo. Adipocyte biology in breast cancer: from silent bystander to active facilitator. Prog. Lipid Res. 69:11–20, 2018.

    Article  Google Scholar 

  9. Chrobak, K. M., D. R. Potter, and J. Tien. Formation of perfused, functional microvascular tubes in vitro. Microvasc. Res. 71:185–196, 2006.

    Article  Google Scholar 

  10. Chun, S. Y., J. O. Lim, E. H. Lee, M. H. Han, Y. S. Ha, J. N. Lee, B. S. Kim, M. J. Park, M. Yeo, B. Jung, and T. G. Kwon. Preparation and characterization of human adipose tissue-derived extracellular matrix, growth factors, and stem cells: a concise review. Tissue Eng. Regen. Med. 16:385–393, 2019.

    Article  Google Scholar 

  11. Colpaert, C., P. Vermeulen, E. Van Marck, and L. Dirix. The presence of a fibrotic focus is an independent predictor of early metastasis in lymph node-negative breast cancer patients. Am. J. Surg. Pathol. 25:1557–1558, 2001.

    Article  Google Scholar 

  12. Costa, A., Y. Kieffer, A. Scholer-Dahirel, F. Pelon, B. Bourachot, M. Cardon, P. Sirven, I. Magagna, L. Fuhrmann, C. Bernard, C. Bonneau, M. Kondratova, I. Kuperstein, A. Zinovyev, A. M. Givel, M. C. Parrini, V. Soumelis, A. Vincent-Salomon, and F. Mechta-Grigoriou. Fibroblast heterogeneity and immunosuppressive environment in human breast cancer. Cancer Cell 33:463–479, 2018.

    Article  Google Scholar 

  13. D’Esposito, V., M. R. Ambrosio, M. Giuliano, S. Cabaro, C. Miele, F. Beguinot, and P. Formisano. Mammary adipose tissue control of breast cancer progression: impact of obesity and diabetes. Front Oncol. 10:1554, 2020.

    Article  Google Scholar 

  14. DeFilippis, R. A., H. Chang, N. Dumont, J. T. Rabban, Y. Y. Chen, G. V. Fontenay, H. K. Berman, M. L. Gauthier, J. Zhao, D. Hu, J. J. Marx, J. A. Tjoe, E. Ziv, M. Febbraio, K. Kerlikowske, B. Parvin, and T. D. Tlsty. CD36 repression activates a multicellular stromal program shared by high mammographic density and tumor tissues. Cancer Discov. 2:826–839, 2012.

    Article  Google Scholar 

  15. Dirat, B., L. Bochet, M. Dabek, D. Daviaud, S. Dauvillier, B. Majed, Y. Y. Wang, A. Meulle, B. Salles, S. Le Gonidec, I. Garrido, G. Escourrou, P. Valet, and C. Muller. Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. 71:2455–2465, 2011.

    Article  Google Scholar 

  16. Duong, M. N., A. Geneste, F. Fallone, X. Li, C. Dumontet, and C. Muller. The fat and the bad: mature adipocytes, key actors in tumor progression and resistance. Oncotarget 8:57622–57641, 2017.

    Article  Google Scholar 

  17. Eto, H., H. Suga, D. Matsumoto, K. Inoue, N. Aoi, H. Kato, J. Araki, and K. Yoshimura. Characterization of structure and cellular components of aspirated and excised adipose tissue. Plast. Reconstr. Surg. 124:1087–1097, 2009.

    Article  Google Scholar 

  18. Flaumenhaft, R., and D. B. Rifkin. The extracellular regulation of growth factor action. Mol. Biol. Cell 3:1057–1065, 1992.

    Article  Google Scholar 

  19. Flynn, L. E. The use of decellularized adipose tissue to provide an inductive microenvironment for the adipogenic differentiation of human adipose-derived stem cells. Biomaterials 31:4715–4724, 2010.

    Article  Google Scholar 

  20. Gao, Y., X. Chen, Q. He, R. C. Gimple, Y. Liao, L. Wang, R. Wu, Q. Xie, J. N. Rich, K. Shen, and Z. Yuan. Adipocytes promote breast tumorigenesis through TAZ-dependent secretion of resistin. Proc. Natl. Acad. Sci. USA 117:33295–33304, 2020.

    Article  Google Scholar 

  21. Gillespie, E. F., M. E. Sorbero, D. A. Hanauer, M. S. Sabel, E. J. Herrmann, L. J. Weiser, C. H. Jagielski, and J. J. Griggs. Obesity and angiolymphatic invasion in primary breast cancer. Ann. Surg. Oncol. 17:752–759, 2010.

    Article  Google Scholar 

  22. Hao, Y., D. Baker, and P. Ten Dijke. TGF-β-mediated epithelial-mesenchymal transition and cancer metastasis. Int. J. Mol. Sci. 20:2767, 2019.

    Article  Google Scholar 

  23. Hume, R. D., L. Berry, S. Reichelt, M. D’Angelo, J. Gomm, R. E. Cameron, and C. J. Watson. An engineered human adipose/collagen model for in vitro breast cancer cell migration studies. Tissue Eng. Part A 24:1309–1319, 2018.

    Article  Google Scholar 

  24. Huo, C. W., G. Chew, P. Hill, D. Huang, W. Ingman, L. Hodson, K. A. Brown, A. Magenau, A. H. Allam, E. McGhee, P. Timpson, M. A. Henderson, E. W. Thompson, and K. Britt. High mammographic density is associated with an increase in stromal collagen and immune cells within the mammary epithelium. Breast Cancer Res. 17:79, 2015.

    Article  Google Scholar 

  25. Iyengar, P., V. Espina, T. W. Williams, Y. Lin, D. Berry, L. A. Jelicks, H. Lee, K. Temple, R. Graves, J. Pollard, N. Chopra, R. G. Russell, R. Sasisekharan, B. J. Trock, M. Lippman, V. S. Calvert, E. F. Petricoin, L. Liotta, E. Dadachova, R. G. Pestell, M. P. Lisanti, P. Bonaldo, and P. E. Scherer. Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment. J. Clin. Invest. 115:1163–1176, 2005.

    Article  Google Scholar 

  26. Jackson, G. W., and D. F. James. The permeability of fibrous porous media. Can. J. Chem. Eng. 64:364–374, 1986.

    Article  Google Scholar 

  27. Jager, M., M. J. Lee, C. Li, S. R. Farmer, S. K. Fried and M. D. Layne. Aortic carboxypeptidase-like protein enhances adipose tissue stromal progenitor differentiation into myofibroblasts and is upregulated in fibrotic white adipose tissue. PLoS ONE 13:e0197777, 2018.

  28. Kakolyris, S., S. B. Fox, M. Koukourakis, A. Giatromanolaki, N. Brown, R. D. Leek, M. Taylor, I. M. Leigh, K. C. Gatter, and A. L. Harris. Relationship of vascular maturation in breast cancer blood vessels to vascular density and metastasis, assessed by expression of a novel basement membrane component, LH39. Br. J. Cancer 82:844–851, 2000.

    Article  Google Scholar 

  29. Kang, J. H., Y. Y. Lee, B. Y. Yu, B. S. Yang, K. H. Cho, D. K. Yoon, and Y. K. Roh. Adiponectin induces growth arrest and apoptosis of MDA-MB-231 breast cancer cell. Arch. Pharm. Res. 28:1263–1269, 2005.

    Article  Google Scholar 

  30. Kim, J., Y. S. Choi, S. Lim, K. Yea, J. H. Yoon, D. J. Jun, S. H. Ha, J. W. Kim, J. H. Kim, P. G. Suh, S. H. Ryu, and T. G. Lee. Comparative analysis of the secretory proteome of human adipose stromal vascular fraction cells during adipogenesis. Proteomics 10:394–405, 2010.

    Article  Google Scholar 

  31. Lee, M. J., and S. K. Fried. Optimal protocol for the differentiation and metabolic analysis of human adipose stromal cells. Methods Enzymol. 538:49–65, 2014.

    Article  Google Scholar 

  32. Lee, Y., W. H. Jung, and J. S. Koo. Adipocytes can induce epithelial-mesenchymal transition in breast cancer cells. Breast Cancer Res. Treat. 153:323–335, 2015.

    Article  Google Scholar 

  33. Li, X., J. Xia, C. T. Nicolescu, M. W. Massidda, T. J. Ryan and J. Tien. Engineering of microscale vascularized fat that responds to perfusion with lipoactive hormones. Biofabrication 11:014101, 2019.

  34. Ling, L., J. A. Mulligan, Y. Ouyang, A. A. Shimpi, R. M. Williams, G. F. Beeghly, B. D. Hopkins, J. A. Spector, S. G. Adie, and C. Fischbach. Obesity-associated adipose stromal cells promote breast cancer invasion through direct cell contact and ECM remodeling. Adv. Funct. Mater. 30:1910650, 2020.

    Article  Google Scholar 

  35. Mao, Y., E. T. Keller, D. H. Garfield, K. Shen, and J. Wang. Stromal cells in tumor microenvironment and breast cancer. Cancer Metastasis Rev. 32:303–315, 2013.

    Article  Google Scholar 

  36. Mertz, D., J. Sentosa, G. Luker, and S. Takayama. Studying adipose tissue in the breast tumor microenvironment in vitro: progress and opportunities. Tissue Eng. Regen. Med. 17:773–785, 2020.

    Article  Google Scholar 

  37. Moll, R., W. W. Franke, D. L. Schiller, B. Geiger, and R. Krepler. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:11–24, 1982.

    Article  Google Scholar 

  38. Motrescu, E. R., S. Blaise, N. Etique, N. Messaddeq, M. P. Chenard, I. Stoll, C. Tomasetto, and M. C. Rio. Matrix metalloproteinase-11/stromelysin-3 exhibits collagenolytic function against collagen VI under normal and malignant conditions. Oncogene 27:6347–6355, 2008.

    Article  Google Scholar 

  39. Padmanaban, V., I. Krol, Y. Suhail, B. M. Szczerba, N. Aceto, J. S. Bader, and A. J. Ewald. E-cadherin is required for metastasis in multiple models of breast cancer. Nature 573:439–444, 2019.

    Article  Google Scholar 

  40. Pallegar, N. K., and S. L. Christian. Adipocytes in the tumour microenvironment. Adv. Exp. Med. Biol. 1234:1–13, 2020.

    Article  Google Scholar 

  41. Pinilla, S., E. Alt, F. J. Abdul Khalek, C. Jotzu, F. Muehlberg, C. Beckmann and Y. H. Song. Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion. Cancer Lett. 284:80-85, 2009.

  42. Piotrowski-Daspit, A. S., A. K. Simi, M. F. Pang, J. Tien, and C. M. Nelson. A 3D culture model to study how fluid pressure and flow affect the behavior of aggregates of epithelial cells. Methods Mol. Biol. 1501:245–257, 2017.

    Article  Google Scholar 

  43. Rabie, E. M., S. X. Zhang, A. P. Kourouklis, A. N. Kilinc, A. K. Simi, D. C. Radisky, J. Tien, and C. M. Nelson. Matrix degradation and cell proliferation are coupled to promote invasion and escape from an engineered human breast microtumor. Integr. Biol. (Camb.). 13:17–29, 2021.

    Article  Google Scholar 

  44. Schäffler, A., J. Schölmerich, and C. Buechler. Mechanisms of disease: adipokines and breast cancer - endocrine and paracrine mechanisms that connect adiposity and breast cancer. Nat. Clin. Pract. Endocrinol. Metab. 3:345–354, 2007.

    Article  Google Scholar 

  45. Seo, B. R., P. Bhardwaj, S. Choi, J. Gonzalez, R. C. Andresen Eguiluz, K. Wang, S. Mohanan, P. G. Morris, B. Du, X. K. Zhou, L. T. Vahdat, A. Verma, O. Elemento, C. A. Hudis, R. M. Williams, D. Gourdon, A. J. Dannenberg and C. Fischbach. Obesity-dependent changes in interstitial ECM mechanics promote breast tumorigenesis. Sci. Transl. Med. 7:301ra130, 2015.

  46. Seyfried, T. N., and L. C. Huysentruyt. On the origin of cancer metastasis. Crit. Rev. Oncog. 18:43–73, 2013.

    Article  Google Scholar 

  47. Song, Y. H., S. H. Shon, M. Shan, A. D. Stroock, and C. Fischbach. Adipose-derived stem cells increase angiogenesis through matrix metalloproteinase-dependent collagen remodeling. Integr. Biol. (Camb.). 8:205–215, 2016.

    Article  Google Scholar 

  48. Stebbing, J., and S. Ngan. Breast cancer (metastatic). BMJ Clin. Evid. 2010:0811, 2010.

    Google Scholar 

  49. Sugihara, H., N. Yonemitsu, S. Toda, S. Miyabara, S. Funatsumaru, and T. Matsumoto. Unilocular fat cells in three-dimensional collagen gel matrix culture. J. Lipid Res. 29:691–697, 1988.

    Article  Google Scholar 

  50. Taliaferro-Smith, L., A. Nagalingam, D. Zhong, W. Zhou, N. K. Saxena, and D. Sharma. LKB1 is required for adiponectin-mediated modulation of AMPK-S6K axis and inhibition of migration and invasion of breast cancer cells. Oncogene 28:2621–2633, 2009.

    Article  Google Scholar 

  51. Tien, J., J. G. Truslow and C. M. Nelson. Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells. PLoS ONE 7:e45191, 2012.

  52. Tien, J., U. Ghani, Y. W. Dance, A. J. Seibel, M. Karakan, K. L. Ekinci and C. M. Nelson. Matrix pore size governs escape of human breast cancer cells from a microtumor to an empty cavity. iScience 23:101673, 2020.

  53. Tien, J., Y. W. Dance, U. Ghani, A. J. Seibel, and C. M. Nelson. Interstitial hypertension suppresses escape of human breast tumor cells via convection of interstitial fluid. Cell. Mol. Bioeng. 14:147–159, 2021.

    Article  Google Scholar 

  54. Tiwari, P., A. Blank, C. Cui, K. Q. Schoenfelt, G. Zhou, Y. Xu, G. Khramtsova, F. Olopade, A. M. Shah, S. A. Khan, M. R. Rosner, and L. Becker. Metabolically activated adipose tissue macrophages link obesity to triple-negative breast cancer. J. Exp. Med. 216:1345–1358, 2019.

    Article  Google Scholar 

  55. Tokunaga, M., M. Inoue, Y. Jiang, R. H. Barnes, D. A. Buchner, and T. H. Chun. Fat depot-specific gene signature and ECM remodeling of Sca1high adipose-derived stem cells. Matrix Biol. 36:28–38, 2014.

    Article  Google Scholar 

  56. Walter, M., S. Liang, S. Ghosh, P. J. Hornsby, and R. Li. Interleukin 6 secreted from adipose stromal cells promotes migration and invasion of breast cancer cells. Oncogene 28:2745–2755, 2009.

    Article  Google Scholar 

  57. Wang, C., C. Gao, K. Meng, H. Qiao and Y. Wang. Human adipocytes stimulate invasion of breast cancer MCF-7 cells by secreting IGFBP-2. PLoS ONE 10:e0119348, 2015.

  58. Wang, J., Y. Cai, F. Yu, Z. Ping, and L. Liu. Body mass index increases the lymph node metastasis risk of breast cancer: a dose-response meta-analysis with 52904 subjects from 20 cohort studies. BMC Cancer 20:601, 2020.

    Article  Google Scholar 

  59. Wang, Y. Y., C. Attané, D. Milhas, B. Dirat, S. Dauvillier, A. Guerard, J. Gilhodes, I. Lazar, N. Alet, V. Laurent, S. Le Gonidec, D. Biard, C. Hervé, F. Bost, G. S. Ren, F. Bono, G. Escourrou, M. Prentki, L. Nieto, P. Valet and C. Muller. Mammary adipocytes stimulate breast cancer invasion through metabolic remodeling of tumor cells. JCI Insight 2:e87489, 2017.

  60. Wellings, S. R., H. M. Jensen, and R. G. Marcum. An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J. Natl. Cancer Inst. 55:231–273, 1975.

    Google Scholar 

  61. Yuan, Y., J. Gao and R. Ogawa. Mechanobiology and mechanotherapy of adipose tissue-effect of mechanical force on fat tissue engineering. Plast. Reconstr. Surg. Glob. Open 3:e578, 2015.

  62. Zhong, J., S. A. Krawczyk, R. Chaerkady, H. Huang, R. Goel, J. S. Bader, G. W. Wong, B. E. Corkey, and A. Pandey. Temporal profiling of the secretome during adipogenesis in humans. J. Proteome Res. 9:5228–5238, 2010.

    Article  Google Scholar 

  63. Zvonic, S., M. Lefevre, G. Kilroy, Z. E. Floyd, J. P. DeLany, I. Kheterpal, A. Gravois, R. Dow, A. White, X. Wu, and J. M. Gimble. Secretome of primary cultures of human adipose-derived stem cells: modulation of serpins by adipogenesis. Mol. Cell. Proteomics 6:18–28, 2007.

    Article  Google Scholar 

Download references

Acknowledgments

We thank Stephen Farmer (Boston Nutrition Obesity Research Center; BNORC) for insightful discussions. This study was funded by award U01 CA214292 from the National Cancer Institute and by award P30 DK046200 from the National Institute of Diabetes and Digestive and Kidney Diseases. Y.W.D. was supported by a training grant from the National Institute of General Medical Sciences (award T32 GM008764) and by a fellowship from the CURE Diversity Research Supplements Program at the National Cancer Institute. Human ASCs were provided by the Adipocyte Core of BNORC.

Conflict of interest

Yoseph W. Dance, Tova Meshulam, Alex J. Seibel, Mackenzie C. Obenreder, Matthew D. Layne, Celeste M. Nelson, and Joe Tien declare that they have no conflict of interest.

Ethical Approval

No human or animal studies were carried out by the authors for this article.

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Boston University, 44 Cummington Mall, Boston, MA, 02215, USA

    Yoseph W. Dance, Alex J. Seibel, Mackenzie C. Obenreder & Joe Tien

  2. Boston Nutrition Obesity Research Center, Boston University School of Medicine, Boston, MA, 02118, USA

    Tova Meshulam

  3. Department of Biochemistry, Boston University School of Medicine, Boston, MA, 02118, USA

    Tova Meshulam & Matthew D. Layne

  4. Department of Chemical and Biological Engineering, Princeton University, 303 Hoyt Laboratory, William Street, Princeton, NJ, 08544, USA

    Celeste M. Nelson

  5. Department of Molecular Biology, Princeton University, Princeton, NJ, 08544, USA

    Celeste M. Nelson

  6. Division of Materials Science and Engineering, Boston University, Boston, MA, 02215, USA

    Joe Tien

Authors
  1. Yoseph W. Dance
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tova Meshulam
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alex J. Seibel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mackenzie C. Obenreder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Matthew D. Layne
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Celeste M. Nelson
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Joe Tien
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Celeste M. Nelson or Joe Tien.

Additional information

Associate Editor Michael R. King oversaw the review of this article.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 1505 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dance, Y.W., Meshulam, T., Seibel, A.J. et al. Adipose Stroma Accelerates the Invasion and Escape of Human Breast Cancer Cells from an Engineered Microtumor. Cel. Mol. Bioeng. 15, 15–29 (2022). https://doi.org/10.1007/s12195-021-00697-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12195-021-00697-6

Keywords

Search

Navigation