Comparison of “Dimensionality” of Cancer Cell Culture in Gelfoam® Histoculture and Matrigel

  • Yasunori Tome
  • Fuminari Uehara
  • Fuminori Kanaya
  • Robert M. Hoffman
Part of the Methods in Molecular Biology book series (MIMB, volume 1760)


Cell and tissue culture can be performed on different substrates such as on plastic, in Matrigel™, and on Gelfoam®, a sponge matrix. Each of these substrates consists of a very different surface, ranging from hard and inflexible, a gel, and a sponge-matrix, respectively. Folkman and Moscona found that cell shape was tightly coupled to proper gene expression. The flexibility of a substrate is important for cells to maintain their optimal shape. Human osteosarcoma cells, stably expressing a fusion protein of av integrin, and green fluorescent protein (GFP), grew as a simple monolayer without any structure formation on the surface of a plastic dish. When the osteosarcoma cells were cultured within Matrigel, the cancer cells formed colonies but no other structures. When the cancer cells were seeded on Gelfoam®, the cells formed 3-dimensional tissue-like structures. These results indicate that Gelfoam® histoculture, unlike Matrigel™ culture, is true 3-dimensional.

Key words

Cancer cells Monolayer Matrigel™ Gelfoam® Green fluorescent protein (GFP) Fluorescence imaging Rendering Dimensionality Aggregation Tissue Structures 


  1. 1.
    Leighton J (1960) The propagation of aggregates of cancer cells: implications for therapy and a simple method of study. Cancer Chemother Rep 9:71–72PubMedGoogle Scholar
  2. 2.
    Leighton J, Kalla R, Turner JM Jr, Fennell RH Jr (1960) Pathogenesis of tumor invasion. II. Aggregate replication. Cancer Res 20:575–586PubMedGoogle Scholar
  3. 3.
    Leighton J (1959) Aggregate replication, a factor in the growth of cancer. Science 129(3347):466–467CrossRefPubMedGoogle Scholar
  4. 4.
    Leighton J, Kalla R, Kline I, Belkin M (1959) Pathogenesis of tumor invasion. I. Interaction between normal tissues and transformed cells in tissue culture. Cancer Res 19:23–27PubMedGoogle Scholar
  5. 5.
    Dawe CJ, Potter M, Leighton J (1958) Progressions of a reticulum-cell sarcoma of the mouse in vivo and in vitro. J Natl Cancer Inst 21:753–781PubMedGoogle Scholar
  6. 6.
    Leighton J (1957) Contributions of tissue culture studies to an understanding of the biology of cancer: a review. Cancer Res 17:929–941PubMedGoogle Scholar
  7. 7.
    Kline I, Leighton J, Belkin M, Orr HC (1957) Some observations on the response of four established human cell strains to hydrocortisone in tissue culture. Cancer Res 17:780–784PubMedGoogle Scholar
  8. 8.
    Leighton J, Kline I, Belkin M, Legallais F, Orr HC (1957) The similarity in histologic appearance of some human cancer and normal cell strains in sponge-matrix tissue culture. Cancer Res 17:359–363PubMedGoogle Scholar
  9. 9.
    Leighton J, Kline I, Belkin M, Orr HC (1957) Effects of a podophyllotoxin derivative on tissue culture systems in which human cancer invades normal tissue. Cancer Res 17:336–344PubMedGoogle Scholar
  10. 10.
    Leighton J, Kline I, Belkin M, Tetenbaum Z (1956) Studies on human cancer using sponge-matrix tissue culture. III. The invasive properties of a carcinoma (strain HeLa) as influenced by temperature variations, by conditioned media, and in contact with rapidly growing chick embryonic tissue. J Natl Cancer Inst 16:1353–1373PubMedGoogle Scholar
  11. 11.
    Leighton J, Kline I, Orr HC (1956) Transformation of normal human fibroblasts into histologically malignant tissue in vitro. Science 123:502CrossRefPubMedGoogle Scholar
  12. 12.
    Leighton J (1954) The growth patterns of some transplantable animal tumors in sponge matrix tissue culture. J Natl Cancer Inst 15:275–293PubMedGoogle Scholar
  13. 13.
    Leighton J, Kline I (1954) Studies on human cancer using sponge matrix tissue culture. II. Invasion of connective tissue by carcinoma (strain HeLa). Tex Rep Biol Med 12:865–873PubMedGoogle Scholar
  14. 14.
    Leighton J (1954) Studies on human cancer using sponge matrix tissue culture. I. The growth patterns of a malignant melanoma, adenocarcinoma of the parotid gland, papillary adenocarcinoma of the thyroid gland, adenocarcinoma of the pancreas, and epidermoid carcinoma of the uterine cervix (Gey's HeLa strain). Tex Rep Biol Med 12:847–864PubMedGoogle Scholar
  15. 15.
    Leighton JA (1951) sponge matrix method for tissue culture; formation of organized aggregates of cells in vitro. J Natl Cancer Inst 12:545–561PubMedGoogle Scholar
  16. 16.
    Jacks T, Weinberg RA (2002) Taking the study of cancer cell survival to a new dimension. Cell 111:923–925CrossRefPubMedGoogle Scholar
  17. 17.
    Abbott A (2003) Cell culture: biology’s new dimension. Nature 424:870–872CrossRefPubMedGoogle Scholar
  18. 18.
    Kleinman HK, McGarvey ML, Hassell JR, Star VL, Cannon FB, Laurie GW, Martin GR (1986) Basement membrane complexes with biological activity. Biochemistry 25:312–318CrossRefPubMedGoogle Scholar
  19. 19.
    Kleinman HK, McGarvey ML, Liotta LA, Robey PG, Tryggvason K, Martin GR (1982) Isolation and characterization of type IV procollagen, laminin, and heparan sulfate proteoglycan from the EHS sarcoma. Biochemistry 21:6188–6193CrossRefPubMedGoogle Scholar
  20. 20.
    Benton G, Kleinman HK, George J, Arnaoutova I (2011) Multiple uses of basement membrane-like matrix (BME/Matrigel™) in vitro and in vivo with cancer cells. Int J Cancer 128:1751–1757CrossRefPubMedGoogle Scholar
  21. 21.
    Folkman J, Moscona A (1978) Role of cell shape in growth control. Nature 273:345–349CrossRefPubMedGoogle Scholar
  22. 22.
    Tome Y, Uehara F, Mii S, Yano S, Zhang L, Sugimoto N, Maehara H, Bouvet M, Tsuchiya H, Kanaya F, Hoffman RM (2014) 3-dimensional tissue is formed from cancer cells in vitro on Gelfoam®, but not on Matrigel™. J Cell Biochem 115:1362–1367CrossRefPubMedGoogle Scholar
  23. 23.
    Luu HH, Kang Q, Park JK, Si W, Luo Q, Jiang W, Yin H, Montag AG, Simon MA, Peabody TD, Haydon RC, Rinker-Schaeffer CW, He TC (2005) An orthotopic model of human osteosarcoma growth and spontaneous pulmonary metastasis. Clin Exp Metastasis 22:319–329CrossRefPubMedGoogle Scholar
  24. 24.
    Cukierman E, Pankov R, Stevens DR, Yamada KM (2001) Taking cell matrix adhesions to the third dimension. Science 294:1708–1712CrossRefPubMedGoogle Scholar
  25. 25.
    Vescio RA, Redfern CH, Nelson TJ, Ugoretz S, Stern PH, Hoffman RM (1987) In vivo-like drug responses of human tumors growing in three-dimensional, gel-supported, primary culture. Proc Natl Acad Sci U S A 84:5029–5033CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Furukawa T, Kubota T, Hoffman RM (1995) Clinical applications of the histoculture drug response assay. Clin Cancer Res 1:305–311PubMedGoogle Scholar
  27. 27.
    Kubota T, Sasano N, Abe O, Nakao I, Kawamura E, Saito T, Endo M, Kimura K, Demura H, Sasano H, Nagura H, Ogawa N, Hoffman RM (1995) The chemosensitivity study group for the histoculture drug-response assay. Potential of the histoculture drug response assay to contribute to cancer patient survival. Clin Cancer Res 1:1537–1543PubMedGoogle Scholar
  28. 28.
    Li L, Margolis LB, Paus R, Hoffman RM (1992) Hair shaft elongation, follicle growth, and spontaneous regression in long-term, gelatin sponge-supported histoculture of human scalp skin. Proc Natl Acad Sci U S A 89:8764–8768CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Glushakova S, Baibakov B, Margolis LB, Zimmerberg J (1995) Infection of human tonsil histocultures: a model for HIV pathogenesis. Nat Med 1:1320–1322CrossRefPubMedGoogle Scholar
  30. 30.
    Mii S, Duong J, Tome Y, Uchugonova A, Liu F, Amoh Y, Saito N, Katsuoka K, Hoffman RM (2013) The role of hair follicle nestin-expressing stem cells during whisker sensory-nerve growth in long-term 3-D culture. J Cell Biochem 114:1674–1684CrossRefPubMedGoogle Scholar
  31. 31.
    Mii S, Uehara F, Yano S, Tran B, Miwa S, Hiroshima Y, Amoh Y, Katsuoka K, Hoffman RM (2013) Nestin-expressing stem cells promote nerve growth in long-term 3-dimensional Gelfoam®-supported histoculture. PLoS One 8:e67153CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Kobayashi HI, Man S, Graham C, Kapitain SJ, Teicher BA, Kerbel RS (1993) Acquired multicellular mediated resistance to alkylating agents in cancer. Proc Natl Acad Sci U S A 90:3294–3298CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yasunori Tome
    • 1
    • 2
    • 3
  • Fuminari Uehara
    • 1
    • 2
    • 3
  • Fuminori Kanaya
    • 3
  • Robert M. Hoffman
    • 1
    • 4
  1. 1.AntiCancer Inc.San DiegoUSA
  2. 2.Department of SurgeryUniversity of CaliforniaSan DiegoUSA
  3. 3.Department of Orthopedic SurgeryGraduate School of Medicine, University of the RyukyusOkinawaJapan
  4. 4.Department of SurgeryUCSDSan DiegoUSA

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