Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 May;67(5):910–921. doi: 10.1038/bjc.1993.170

Complementation of two related tumour cell classes during experimental metastasis tagged with different histochemical marker genes.

W C Lin 1, K L O'Connor 1, L A Culp 1
PMCID: PMC1968424  PMID: 8494724

Abstract

Intercellular complementation during tumour development and metastasis was analysed for two different oncogene (ras or sis) transformants of Balb/c 3T3 cells, tagged with different histochemical marker genes (lacZ or ALP to generate LZEJ or APSI cells, respectively), by localising them after their co-injection with specific double-staining protocols. This model evaluates whether limited progression of each tumour class can be facilitated reciprocally during co-localisation and co-growth in nude mice by taking advantage of the sensitivity of the histochemical marker genes for localising them. After intravenous co-injection of equal numbers of both cells to analyse experimental metastasis, most foci transiently established in the lung for several hours were comprised of only one cell class. However, a significant fraction of foci contained both cell types, as identified in double-stained whole-lung tissues and in lung sections. Evidence was obtained that LZEJ cells increase the survivability and subsequent growth of APSI-containing micrometastases during co-localisation in lung, when compared to APSI cells injected alone. Conversely, APSI cells facilitate expansion of LZEJ cells from micrometastatic foci into overt-metastatic nodules in the lung. These analyses reveal reciprocity during experimental metastasis by two related tumour cell classes derived from the same parental cell.

Full text

PDF
910

Images in this article

912Figure 1
on p.912
913Figure 2
on p.913
915Figure 3
on p.915
916Figure 4
on p.916
917Figure 5
on p.917
918Figure 6
on p.918

Selected References

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

  1. Aslakson C. J., Rak J. W., Miller B. E., Miller F. R. Differential influence of organ site on three subpopulations of a single mouse mammary tumor at two distinct steps in metastasis. Int J Cancer. 1991 Feb 1;47(3):466–472. doi: 10.1002/ijc.2910470327. [DOI] [PubMed] [Google Scholar]
  2. Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
  3. Baroffio A., Dupin E., Le Douarin N. M. Clone-forming ability and differentiation potential of migratory neural crest cells. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5325–5329. doi: 10.1073/pnas.85.14.5325. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beckmann M. P., Betsholtz C., Heldin C. H., Westermark B., Di Marco E., Di Fiore P. P., Robbins K. C., Aaronson S. A. Comparison of biological properties and transforming potential of human PDGF-A and PDGF-B chains. Science. 1988 Sep 9;241(4871):1346–1349. doi: 10.1126/science.2842868. [DOI] [PubMed] [Google Scholar]
  5. Breillout F., Antoine E., Lascaux V., Rolland Y., Poupon M. F. Promotion of micrometastasis proliferation in a rat rhabdomyosarcoma model by epidermal growth factor. J Natl Cancer Inst. 1989 May 3;81(9):702–705. doi: 10.1093/jnci/81.9.702. [DOI] [PubMed] [Google Scholar]
  6. Bronzert D. A., Pantazis P., Antoniades H. N., Kasid A., Davidson N., Dickson R. B., Lippman M. E. Synthesis and secretion of platelet-derived growth factor by human breast cancer cell lines. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5763–5767. doi: 10.1073/pnas.84.16.5763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cavanaugh P. G., Nicolson G. L. Purification and some properties of a lung-derived growth factor that differentially stimulates the growth of tumor cells metastatic to the lung. Cancer Res. 1989 Jul 15;49(14):3928–3933. [PubMed] [Google Scholar]
  8. Egan S. E., Jarolim L., Rogelj S., Spearman M., Wright J. A., Greenberg A. H. Growth factor modulation of metastatic lung colonization. Anticancer Res. 1990 Sep-Oct;10(5A):1341–1346. [PubMed] [Google Scholar]
  9. Egan S. E., McClarty G. A., Jarolim L., Wright J. A., Spiro I., Hager G., Greenberg A. H. Expression of H-ras correlates with metastatic potential: evidence for direct regulation of the metastatic phenotype in 10T1/2 and NIH 3T3 cells. Mol Cell Biol. 1987 Feb;7(2):830–837. doi: 10.1128/mcb.7.2.830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fidler I. J., Balch C. M. The biology of cancer metastasis and implications for therapy. Curr Probl Surg. 1987 Mar;24(3):129–209. doi: 10.1016/0011-3840(87)90002-5. [DOI] [PubMed] [Google Scholar]
  11. Fraizer G. C., Bowen-Pope D. F., Seifert R. A., Vogel A. M. Association of increased platelet-derived growth factor secretion and retroviral expression in transformed mouse and human cells. Cancer Res. 1988 Sep 1;48(17):4874–4880. [PubMed] [Google Scholar]
  12. Goustin A. S., Leof E. B., Shipley G. D., Moses H. L. Growth factors and cancer. Cancer Res. 1986 Mar;46(3):1015–1029. [PubMed] [Google Scholar]
  13. Hart I. R., Goode N. T., Wilson R. E. Molecular aspects of the metastatic cascade. Biochim Biophys Acta. 1989 Jul 28;989(1):65–84. doi: 10.1016/0304-419x(89)90035-8. [DOI] [PubMed] [Google Scholar]
  14. Hart I. R., Saini A. Biology of tumour metastasis. Lancet. 1992 Jun 13;339(8807):1453–1457. doi: 10.1016/0140-6736(92)92039-i. [DOI] [PubMed] [Google Scholar]
  15. Henthorn P., Zervos P., Raducha M., Harris H., Kadesch T. Expression of a human placental alkaline phosphatase gene in transfected cells: use as a reporter for studies of gene expression. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6342–6346. doi: 10.1073/pnas.85.17.6342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Heppner G. H., Miller B. E. Tumor heterogeneity: biological implications and therapeutic consequences. Cancer Metastasis Rev. 1983;2(1):5–23. doi: 10.1007/BF00046903. [DOI] [PubMed] [Google Scholar]
  17. Heppner G. H. Tumor heterogeneity. Cancer Res. 1984 Jun;44(6):2259–2265. [PubMed] [Google Scholar]
  18. Johnsson A., Betsholtz C., von der Helm K., Heldin C. H., Westermark B. Platelet-derived growth factor agonist activity of a secreted form of the v-sis oncogene product. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1721–1725. doi: 10.1073/pnas.82.6.1721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Keating M. T., Williams L. T. Autocrine stimulation of intracellular PDGF receptors in v-sis-transformed cells. Science. 1988 Feb 19;239(4842):914–916. doi: 10.1126/science.2829358. [DOI] [PubMed] [Google Scholar]
  20. Lin W. C., Culp L. A. Altered establishment/clearance mechanisms during experimental micrometastasis with live and/or disabled bacterial lacZ-tagged tumor cells. Invasion Metastasis. 1992;12(3-4):197–209. [PubMed] [Google Scholar]
  21. Lin W. C., Culp L. A. Selectable plasmid vectors with alternative and ultrasensitive histochemical marker genes. Biotechniques. 1991 Sep;11(3):344-8, 350-1. [PubMed] [Google Scholar]
  22. Lin W. C., Pretlow T. P., Pretlow T. G., 2nd, Culp L. A. Bacterial lacZ gene as a highly sensitive marker to detect micrometastasis formation during tumor progression. Cancer Res. 1990 May 1;50(9):2808–2817. [PubMed] [Google Scholar]
  23. Lin W. C., Pretlow T. P., Pretlow T. G., 2nd, Culp L. A. High-resolution analyses of two different classes of tumor cells in situ tagged with alternative histochemical marker genes. Am J Pathol. 1992 Dec;141(6):1331–1342. [PMC free article] [PubMed] [Google Scholar]
  24. Lin W. C., Pretlow T. P., Pretlow T. G., 3rd, Culp L. A. Development of micrometastases: earliest events detected with bacterial lacZ gene-tagged tumor cells. J Natl Cancer Inst. 1990 Sep 19;82(18):1497–1503. doi: 10.1093/jnci/82.18.1497. [DOI] [PubMed] [Google Scholar]
  25. Maghazachi A. A., Herberman R. B., Vujanovic N. L., Hiserodt J. C. In vivo distribution and tissue localization of highly purified rat lymphokine-activated killer (LAK) cells. Cell Immunol. 1988 Aug;115(1):179–194. doi: 10.1016/0008-8749(88)90172-4. [DOI] [PubMed] [Google Scholar]
  26. Miller B. E., Miller F. R., Leith J., Heppner G. H. Growth interaction in vivo between tumor subpopulations derived from a single mouse mammary tumor. Cancer Res. 1980 Nov;40(11):3977–3981. [PubMed] [Google Scholar]
  27. Miller B. E., Miller F. R., Wilburn D., Heppner G. H. Dominance of a tumor subpopulation line in mixed heterogeneous mouse mammary tumors. Cancer Res. 1988 Oct 15;48(20):5747–5753. [PubMed] [Google Scholar]
  28. Miller F. R., Heppner G. H. Cellular interactions in metastasis. Cancer Metastasis Rev. 1990 Jul;9(1):21–34. doi: 10.1007/BF00047586. [DOI] [PubMed] [Google Scholar]
  29. Moffett B. F., Baban D., Bao L., Tarin D. Fate of clonal lineages during neoplasia and metastasis studied with an incorporated genetic marker. Cancer Res. 1992 Apr 1;52(7):1737–1743. [PubMed] [Google Scholar]
  30. Nicolson G. L. Cancer metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites. Biochim Biophys Acta. 1988 Nov 15;948(2):175–224. doi: 10.1016/0304-419x(88)90010-8. [DOI] [PubMed] [Google Scholar]
  31. Pozzatti R., McCormick M., Thompson M. A., Khoury G. The E1a gene of adenovirus type 2 reduces the metastatic potential of ras-transformed rat embryo cells. Mol Cell Biol. 1988 Jul;8(7):2984–2988. doi: 10.1128/mcb.8.7.2984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Radinsky R., Culp L. A. Clonal dominance of select subsets of viral Kirsten ras(+)-transformed 3T3 cells during tumor progression. Int J Cancer. 1991 Apr 22;48(1):148–159. doi: 10.1002/ijc.2910480126. [DOI] [PubMed] [Google Scholar]
  33. Radinsky R., Kraemer P. M., Raines M. A., Kung H. J., Culp L. A. Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5143–5147. doi: 10.1073/pnas.84.15.5143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sugita K., Koizumi K., Yoshida H. Morphological reversion of sis-transformed NIH3T3 cells by trichostatin A. Cancer Res. 1992 Jan 1;52(1):168–172. [PubMed] [Google Scholar]
  35. Tsuruo T., Watanabe M., Oh-hara T. Stimulation of the growth of metastatic clones of mouse colon adenocarcinoma 26 in vitro by platelet-derived growth factor. Jpn J Cancer Res. 1989 Feb;80(2):136–140. doi: 10.1111/j.1349-7006.1989.tb02281.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Weinberg R. A. The action of oncogenes in the cytoplasm and nucleus. Science. 1985 Nov 15;230(4727):770–776. doi: 10.1126/science.2997917. [DOI] [PubMed] [Google Scholar]
  37. Zhan X., Goldfarb M. Growth factor requirements of oncogene-transformed NIH 3T3 and BALB/c 3T3 cells cultured in defined media. Mol Cell Biol. 1986 Oct;6(10):3541–3544. doi: 10.1128/mcb.6.10.3541. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES