Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Jul;72(1):10–16. doi: 10.1038/bjc.1995.269

Comparison of basic fibroblast growth factor levels in clone A human colon cancer cells in vitro with levels in xenografted tumours.

L P McCarty 3rd 1, S M Karr 1, B Z Harris 1, S G Michelson 1, J T Leith 1
PMCID: PMC2034148  PMID: 7599036

Abstract

We measured levels of basic fibroblast growth factor (FGF-2) in human colon cancer cells (clone A) in vitro and in xenografted solid tumours using a commercial enzyme-linked immunoassay. In Vitro, levels in unfed plateau phase or exponentially growing cells were low, averaging respectively about 2 and 8 pg 10(-6) cells. However, when solid tumours (average volumes 787 mm3) were cut into halves and either enzymatically disaggregated to obtain a cellular fraction or extracted in toto, levels were much higher. In the cellular fraction, values averaged 110 pg 10(-6) cells, while in whole tumour extracts, average values were 24 pg mg-1 tumour tissue. These results indicate that growth factor levels in solid neoplasms may differ markedly from those predicted from in vitro measurements. We hypothesise that the apparent increase in FGF-2 levels in vivo results primarily from the presence of a significant fraction of host cells (in particular, macrophages, which may contain high levels of FGF-2) within xenografted clone A neoplasms.

Full text

PDF
10

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baird A., Mormède P., Böhlen P. Immunoreactive fibroblast growth factor in cells of peritoneal exudate suggests its identity with macrophage-derived growth factor. Biochem Biophys Res Commun. 1985 Jan 16;126(1):358–364. doi: 10.1016/0006-291x(85)90614-x. [DOI] [PubMed] [Google Scholar]
  2. Bliven S. F., Schneiderman T. E., Leith J. T. Cell cycle responses of heterogeneous human colon adenocarcinoma subpopulations to X-irradiation. Cell Tissue Kinet. 1987 Sep;20(5):473–483. doi: 10.1111/j.1365-2184.1987.tb01356.x. [DOI] [PubMed] [Google Scholar]
  3. Bost L. M., Hjelmeland L. M. Cell density regulates differential production of bFGF transcripts. Growth Factors. 1993;9(3):195–203. doi: 10.3109/08977199309010832. [DOI] [PubMed] [Google Scholar]
  4. Calabresi P., Dexter D. L., Heppner G. H. Clinical and pharmacological implications of cancer cell differentiation and heterogeneity. Biochem Pharmacol. 1979 Jun 15;28(12):1933–1941. doi: 10.1016/0006-2952(79)90647-6. [DOI] [PubMed] [Google Scholar]
  5. D'Amore P. A., Smith S. R. Growth factor effects on cells of the vascular wall: a survey. Growth Factors. 1993;8(1):61–75. doi: 10.3109/08977199309029135. [DOI] [PubMed] [Google Scholar]
  6. Dexter D. L., Spremulli E. N., Fligiel Z., Barbosa J. A., Vogel R., VanVoorhees A., Calabresi P. Heterogeneity of cancer cells from a single human colon carcinoma. Am J Med. 1981 Dec;71(6):949–956. doi: 10.1016/0002-9343(81)90312-0. [DOI] [PubMed] [Google Scholar]
  7. Esko J. D., Rostand K. S., Weinke J. L. Tumor formation dependent on proteoglycan biosynthesis. Science. 1988 Aug 26;241(4869):1092–1096. doi: 10.1126/science.3137658. [DOI] [PubMed] [Google Scholar]
  8. Evans R. Effect of X-irradiation on host-cell infiltration and growth of a murine fibrosarcoma. Br J Cancer. 1977 May;35(5):557–566. doi: 10.1038/bjc.1977.89. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Frautschy S. A., Walicke P. A., Baird A. Localization of basic fibroblast growth factor and its mRNA after CNS injury. Brain Res. 1991 Jul 12;553(2):291–299. doi: 10.1016/0006-8993(91)90837-l. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Freyer J. P. Role of necrosis in regulating the growth saturation of multicellular spheroids. Cancer Res. 1988 May 1;48(9):2432–2439. [PubMed] [Google Scholar]
  11. Goto F., Goto K., Weindel K., Folkman J. Synergistic effects of vascular endothelial growth factor and basic fibroblast growth factor on the proliferation and cord formation of bovine capillary endothelial cells within collagen gels. Lab Invest. 1993 Nov;69(5):508–517. [PubMed] [Google Scholar]
  12. Greisler H. P., Henderson S. C., Lam T. M. Basic fibroblast growth factor production in vitro by macrophages exposed to Dacron and polyglactin 910. J Biomater Sci Polym Ed. 1993;4(5):415–430. doi: 10.1163/156856293x00096. [DOI] [PubMed] [Google Scholar]
  13. Gross J. L., Herblin W. F., Dusak B. A., Czerniak P., Diamond M. D., Sun T., Eidsvoog K., Dexter D. L., Yayon A. Effects of modulation of basic fibroblast growth factor on tumor growth in vivo. J Natl Cancer Inst. 1993 Jan 20;85(2):121–131. doi: 10.1093/jnci/85.2.121. [DOI] [PubMed] [Google Scholar]
  14. Hannan R. L., Kourembanas S., Flanders K. C., Rogelj S. J., Roberts A. B., Faller D. V., Klagsbrun M. Endothelial cells synthesize basic fibroblast growth factor and transforming growth factor beta. Growth Factors. 1988;1(1):7–17. doi: 10.3109/08977198809000242. [DOI] [PubMed] [Google Scholar]
  15. Hauptmann S., Zwadlo-Klarwasser G., Jansen M., Klosterhalfen B., Kirkpatrick C. J. Macrophages and multicellular tumor spheroids in co-culture: a three-dimensional model to study tumor-host interactions. Evidence for macrophage-mediated tumor cell proliferation and migration. Am J Pathol. 1993 Nov;143(5):1406–1415. [PMC free article] [PubMed] [Google Scholar]
  16. Hughes S. E., Crossman D., Hall P. A. Expression of basic and acidic fibroblast growth factors and their receptor in normal and atherosclerotic human arteries. Cardiovasc Res. 1993 Jul;27(7):1214–1219. doi: 10.1093/cvr/27.7.1214. [DOI] [PubMed] [Google Scholar]
  17. Jenks S. Angiogenesis research spreads to clinic. J Natl Cancer Inst. 1994 May 18;86(10):742–743. doi: 10.1093/jnci/86.10.742. [DOI] [PubMed] [Google Scholar]
  18. Leith J. T., Michelson S. Effects of administration of basic fibroblast growth factor on hypoxic fractions in xenografted DLD-2 human tumours: time dependence. Br J Cancer. 1993 Oct;68(4):727–731. doi: 10.1038/bjc.1993.418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Leith J. T., Padfield G., Faulkner L. E., Quinn P., Michelson S. Effects of feeder cells on the X-ray sensitivity of human colon cancer cells. Radiother Oncol. 1991 May;21(1):53–59. doi: 10.1016/0167-8140(91)90341-d. [DOI] [PubMed] [Google Scholar]
  20. Leith J. T., Padfield G., Faulkner L., Michelson S. Hypoxic fractions in xenografted human colon tumors. Cancer Res. 1991 Oct 1;51(19):5139–5143. [PubMed] [Google Scholar]
  21. Leith J. T., Papa G., Quaranto L., Michelson S. Modification of the volumetric growth responses and steady-state hypoxic fractions of xenografted DLD-2 human colon carcinomas by administration of basic fibroblast growth factor or suramin. Br J Cancer. 1992 Aug;66(2):345–348. doi: 10.1038/bjc.1992.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Liaw L., Schwartz S. M. Microtubule disruption stimulates DNA synthesis in bovine endothelial cells and potentiates cellular response to basic fibroblast growth factor. Am J Pathol. 1993 Sep;143(3):937–948. [PMC free article] [PubMed] [Google Scholar]
  23. Logan A., Frautschy S. A., Gonzalez A. M., Baird A. A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of its high-affinity receptors (flg) following a localized cortical brain injury. J Neurosci. 1992 Oct;12(10):3828–3837. doi: 10.1523/JNEUROSCI.12-10-03828.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Michelson S., Leith J. T. Growth factors and growth control of heterogeneous cell populations. Bull Math Biol. 1993 Sep;55(5):993–1011. doi: 10.1007/BF02460696. [DOI] [PubMed] [Google Scholar]
  25. Milas L., Wike J., Hunter N., Volpe J., Basic I. Macrophage content of murine sarcomas and carcinomas: associations with tumor growth parameters and tumor radiocurability. Cancer Res. 1987 Feb 15;47(4):1069–1075. [PubMed] [Google Scholar]
  26. Moscatelli D., Presta M., Joseph-Silverstein J., Rifkin D. B. Both normal and tumor cells produce basic fibroblast growth factor. J Cell Physiol. 1986 Nov;129(2):273–276. doi: 10.1002/jcp.1041290220. [DOI] [PubMed] [Google Scholar]
  27. Motoo Y., Sawabu N., Nakanuma Y. Expression of epidermal growth factor and fibroblast growth factor in human hepatocellular carcinoma: an immunohistochemical study. Liver. 1991 Oct;11(5):272–277. doi: 10.1111/j.1600-0676.1991.tb00529.x. [DOI] [PubMed] [Google Scholar]
  28. Murono E. P., Washburn A. L., Goforth D. P., Wu N. Evidence for basic fibroblast growth factor receptors in cultured immature Leydig cells. Mol Cell Endocrinol. 1992 Oct;88(1-3):39–45. doi: 10.1016/0303-7207(92)90007-s. [DOI] [PubMed] [Google Scholar]
  29. Murthy U., Anzano M. A., Greig R. G. Expression of TGF-alpha/EGF and TGF-beta receptors in human colon carcinoma cell lines. Int J Cancer. 1989 Jul 15;44(1):110–115. doi: 10.1002/ijc.2910440120. [DOI] [PubMed] [Google Scholar]
  30. Nakajima M., Morikawa K., Fabra A., Bucana C. D., Fidler I. J. Influence of organ environment on extracellular matrix degradative activity and metastasis of human colon carcinoma cells. J Natl Cancer Inst. 1990 Dec 19;82(24):1890–1898. doi: 10.1093/jnci/82.24.1890. [DOI] [PubMed] [Google Scholar]
  31. Nguyen M., Watanabe H., Budson A. E., Richie J. P., Hayes D. F., Folkman J. Elevated levels of an angiogenic peptide, basic fibroblast growth factor, in the urine of patients with a wide spectrum of cancers. J Natl Cancer Inst. 1994 Mar 2;86(5):356–361. doi: 10.1093/jnci/86.5.356. [DOI] [PubMed] [Google Scholar]
  32. Pallavicini M. G., Lalande M. E., Miller R. G., Hill R. P. Cell cycle distribution of chronically hypoxic cells and determination of the clonogenic potential of cells accumulated in G2 + M phases after irradiation of a solid tumor in vivo. Cancer Res. 1979 Jun;39(6 Pt 1):1891–1897. [PubMed] [Google Scholar]
  33. Pepper M. S., Ferrara N., Orci L., Montesano R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem Biophys Res Commun. 1992 Dec 15;189(2):824–831. doi: 10.1016/0006-291x(92)92277-5. [DOI] [PubMed] [Google Scholar]
  34. Porschen R., Porschen W., Mühlensiepen H., Feinendegen L. E. Cell loss from viable and necrotic tumour regions measured by 125I-UdR. Cell Tissue Kinet. 1983 Nov;16(6):549–556. [PubMed] [Google Scholar]
  35. Rice G. C., Spiro I. J., Ling C. C. Detection of S-phase overreplication following chronic hypoxia using a monoclonal anti-BrdUrd. Int J Radiat Oncol Biol Phys. 1985 Oct;11(10):1817–1822. doi: 10.1016/0360-3016(85)90038-0. [DOI] [PubMed] [Google Scholar]
  36. Shweiki D., Itin A., Soffer D., Keshet E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature. 1992 Oct 29;359(6398):843–845. doi: 10.1038/359843a0. [DOI] [PubMed] [Google Scholar]
  37. Siemann D. W., Lord E. M., Keng P. C., Wheeler K. T. Cell subpopulations dispersed from solid tumours and separated by centrifugal elutriation. Br J Cancer. 1981 Jul;44(1):100–108. doi: 10.1038/bjc.1981.154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Soutter A. D., Nguyen M., Watanabe H., Folkman J. Basic fibroblast growth factor secreted by an animal tumor is detectable in urine. Cancer Res. 1993 Nov 1;53(21):5297–5299. [PubMed] [Google Scholar]
  39. Vlodavsky I., Fuks Z., Ishai-Michaeli R., Bashkin P., Levi E., Korner G., Bar-Shavit R., Klagsbrun M. Extracellular matrix-resident basic fibroblast growth factor: implication for the control of angiogenesis. J Cell Biochem. 1991 Feb;45(2):167–176. doi: 10.1002/jcb.240450208. [DOI] [PubMed] [Google Scholar]
  40. West C. M., Keng P. C., Siemann D. W., Sutherland R. M. A human colon adenocarcinoma xenograft--radiation response, cellular composition, and tumor disaggregation. J Natl Cancer Inst. 1987 Feb;78(2):371–376. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES