Autocrine down-regulation of basic fibroblast growth factor receptors causes mitotoxin resistance in a human melanoma cell line.

The ability of melanoma to develop resistance to mitotoxins, growth-factor-directed anti-neoplastic agents that offer potential for the treatment of this highly refractory disease, may limit therapeutic efficacy. To address this problem, we developed a subcloned human melanoma cell line that is resistant to the mitotoxin composed of basic fibroblast growth factor conjugated to the ribosome-inactivating protein saporin. Resistance was caused by autocrine FGF ligands, which down-regulate bFGF receptors and reduce bFGF-saporin binding. Inhibiting the autocrine loop with suramin or with neutralizing antibodies to FGF up-regulated receptors and decreased resistance in vitro. Furthermore, suramin restored sensitivity in resistant tumor xenografts. These results suggest the potential of therapeutic modalities combining agents that neutralize growth factors with receptor-directed mitotoxins for targeting malignant melanoma either to prevent emergence of resistance or to circumvent resistance once it occurs.

• Publication year

  1995

• Venue

  Journal of Investigative Dermatology

• Publication date

  1995-06-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1111/1523-1747.EP12606193PMID 7769258
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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