Hypoxia: dual effect on the expression of transferrin receptor in human melanoma A375 cell line

Exp Dermatol. 2007 Nov;16(11):899-904. doi: 10.1111/j.1600-0625.2007.00601.x.

Abstract

Background: Over-expression of transferrin receptor (TfR) is a common feature of human malignancies. Therapeutic strategies designed to interfere with tumor iron metabolism have targeted TfR. In previous studies, our laboratory successfully constructed the human-mouse chimeric antibody against TfR and it displayed a tumor-specificity distribution, and has a strong anti-tumor effect. We also found that there were still some limitations to anti-tumor effect in vivo. Oxygen and iron have a very tight relationship, and hypoxia is considered a fundamentally important characteristic of the tumor microenvironment. To exploit the target molecule TfR more rationally and effectively, we were prompted to explore TfR expression under hypoxia.

Objective: To examine the expressing alteration of TfR of human melanoma A375 cell line under hypoxia at various time points (0, 12, 24, 36, 48 and 60 h).

Design: The expressing alteration of TfR of A375 cell line under hypoxia at various time points (0, 12, 24, 36, 48 and 60 h) was assayed by flow cytometry, real-time RT-PCR and Western blot.

Results: Hypoxia has dual effect on the expression of TfR in human melanoma A375 cell line.

Conclusions: These findings may have important implications for more rational, individualized gene-based therapy using TfR as target receptor in melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / physiology
  • Cell Hypoxia / physiology*
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Inhibitor of Apoptosis Proteins / genetics
  • Inhibitor of Apoptosis Proteins / metabolism
  • Iron / metabolism
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Melanoma / physiopathology
  • Oxygen / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Transferrin / genetics
  • Receptors, Transferrin / metabolism*
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / physiopathology
  • Time Factors
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Inhibitor of Apoptosis Proteins
  • RNA, Messenger
  • Receptors, Transferrin
  • bcl-2-Associated X Protein
  • Iron
  • Oxygen