Skip to main content
Log in

Activated leukocyte cell adhesion molecule (ALCAM) and annexin II are involved in the metastatic progression of tumor cells after chemotherapy with Adriamycin

  • Published:
Clinical & Experimental Metastasis Aims and scope Submit manuscript

Abstract

Metastasis frequently occurs during and/or after chemotherapy resulting in failure. This suggests that inadequate chemotherapy promotes the emergence of more malignant tumor cells with metastatic potential. However, it is not determined how chemotherapy could promote the metastatic progression of tumor cells. In this study, we isolated highly metastatic clones from the tumors treated with ADR using an in vivo experimental model, in which non-metastatic tumor cells were inoculated s.c. in mice, treated with or without Adriamycin and then culture lines were re-established from the tumors. Then we isolated cDNAs for activated leukocyte cell adhesion molecule (ALCAM), osteopontin, and annexin II as candidates for metastasis-promoting genes with the use of a PCR-based subtraction method. Further we examined the metastatic potential of transfectants over-expressing ALCAM, osteopontin, or annexin II and combinations of them. Metastasis to the lung was observed in the mice where transfectants over-expressing ALCAM plus annexin II had been inoculated via tail vein. These results suggest that the over-expression of ALCAM and annexin II play a role in the metastatic progression after chemotherapy with ADR.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Poste G., Fidler IJ. The pathogenesis of cancer metastasis. Nature 1980; 283: 139–46.

    Google Scholar 

  2. Liotta LA. Gene products which play a role in cancer invasion and metastasis. Breast Cancer Res 1988; 11: 113–24.

    Google Scholar 

  3. Nicolson GL. Cancer metastasis: tumor cell and host organ properties important in metastasis to specific secondary sites. Biochem. Biophys. Acta 1988; 948: 175–224.

    Google Scholar 

  4. Humphries MJ, Olden K, Yamada KM. A synthetic peptide from fibronectin inhibits experimental metastasis of murine melanoma cells. Science 1986; 233: 467–70.

    Google Scholar 

  5. Liotta, LA. Tumor invasion and metastasis-role of the extracellular matrix. Cancer Res 1986; 46: 1–7.

    Google Scholar 

  6. Nicolson, GL. Metastatic tumor cell interactions with endothelium, basement membrane and tissue. Curr Opin Cell Biol 1989; 1: 1009–19.

    Google Scholar 

  7. Pauli BU, Augustin-Voss HG, El-Sabban M et al. Organ-preference of metastasis. The role of endothelial cell adhesion molecules. Cancer Metastasis Rev 1990; 9: 175–89.

    Google Scholar 

  8. Stefani S, Elles RW, Abbate J. Hydroxyurea and radiotherapy in head and neck cancer. Radiology 1971; 101: 391–6.

    Google Scholar 

  9. Kerbel RS and Davies AJS. Facilitation of tumour progression by cancer therapy. Lancet 1982; 302: 977–8.

    Google Scholar 

  10. Slotman GJ, Mohit T, Raina S et al. The incidence of metastases after multimodal therapy for cancer of the head and neck. Cancer 1984; 54: 2009–2014.

    Google Scholar 

  11. McMillan TJ, Hart IR. Can chemotherapy enhance the malignant behaviour of tumours? Cancer Metastasis Rev. 1987; 6: 503–20.

    Google Scholar 

  12. Okada F, Hosokawa M, Hasegawa J et al. Regression mechanisms of mouse fibrosarcoma cells after exposure to quercetin: diminution of tumorigenicity with a corresponding decrease in the production of prostaglandin E2. Cancer Immunol Immunother 1990; 31: 358–64.

    Google Scholar 

  13. Wang Z and Brown DD. A gene expression screen. Proc Natl Acad Sci USA 1991; 88: 11505–9.

    Google Scholar 

  14. Patel DD, Wee SF, Whichard LP et al. Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells. J Exp Med 1995; 181: 1563–8.

    Google Scholar 

  15. Aruffo A, Bowen MA, Patel DD et al. CD6-ligand interactions: a paradigm for SRCR domain function? Immunol Today 1997; 18: 498–504.

    Google Scholar 

  16. Bowen MA, Bajorath J, D’Egidio M et al. Characterization of mouse ALCAM (CD166): the CD6-binding domain is conserved in different homologs and mediates cross-species binding. Eur J Immunol 1997; 27: 1469–78.

    Google Scholar 

  17. Degen WG, van Kempen LC, Gijzen EC et al. MEMD, a new cell adhesion molecule in metastasizing human melanoma cell lines, is identical to ALCAM (activated leukocyte cell adhesion molecule). Am J Pathol 1998; 152: 805–13.

    Google Scholar 

  18. Niki I, Yokokura H, Sudo T et al. Ca2+ signaling and intracellular Ca2+ binding proteins. J Biochem (Tokyo) 1996; 120: 685–98.

    Google Scholar 

  19. Biener Y, Feinstein R, Mayak M et al. Annexin II is a novel player in insulin signal transduction. Possible association between annexin II phosphorylation and insulin receptor internalization. J Biol Chem 1996; 271: 29489–96.

    Google Scholar 

  20. Schlaepfer DD and Haigler HT. Expression of annexins as a function of cellular growth state. J Cell Biol 1990; 111: 229–38.

    Google Scholar 

  21. Kumble KD, Hirota M, Pour PM et al. Enhanced levels of annexins in pancreatic carcinoma cells of Syrian hamsters and their intrapancreatic allografts. Cancer Res 1992; 52: 163–7.

    Google Scholar 

  22. Vishwanatha JK, Chiang Y, Kumble KD et al. Enhanced expression of annexin II in human pancreatic carcinoma cells and primary pancreatic cancers. Carcinogenesis 1993; 14: 2575–9.

    Google Scholar 

  23. Yeatman TJ, Updyke TV, Kaetzel MA et al. Expression of annexins on the cell surfaces of non-metastatic and metastatic human and rodent tumor cells. Clin Exp Metastasis 1993; 11: 37–44.

    Google Scholar 

  24. Pencil SD, Toh Y, Nicolson GL. Candidate metastasis-associated genes of the rat 13762NF mammary adenocarcinoma. Breast Cancer Res Treat 1993; 25: 165–74.

    Google Scholar 

  25. Pencil SD and Toth M Elevated levels of annexin I protein in vitro and in vivo in rat and human mammary adenocarcinoma. Clin Exp Metastasis 1998; 16: 113–21.

    Google Scholar 

  26. Hajjar KA, Jacovina AT, Chacko J. An endothelial cell receptor for plasminogen/tissue plasminogen activator. I. Identity with annexin II. J Biol Chem 1994; 269: 21191–97.

    Google Scholar 

  27. Paciucci R, Tora M, Diaz VM et al. The plasminogen activator system in pancreas cancer: role of t-PA in the invasive potential in vitro. Oncogene 1998; 16: 625–33.

    Google Scholar 

  28. Boid D. Invasion and metastasis. Cancer Metastasis Rev 1996; 15: 77–89.

    Google Scholar 

  29. Goldberg GI, Frisch SM, He C et al. Secreted proteases. Regulation of their activity and their possible role in metastasis. Ann NY Acad Sci 1990; 580: 375–84.

    Google Scholar 

  30. DeClerck YA, Imren S, Montgomery AM et al. Proteases and protease inhibitors in tumor progression. Adv Exp Med Biol 1997; 425: 89–97.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Choi, S., Kobayashi, M., Wang, J. et al. Activated leukocyte cell adhesion molecule (ALCAM) and annexin II are involved in the metastatic progression of tumor cells after chemotherapy with Adriamycin. Clin Exp Metastasis 18, 45–50 (2000). https://doi.org/10.1023/A:1026507713080

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1026507713080

Navigation