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Tumor progression in vitro: tumor-promoter-induced reversible decrease in natural immune susceptibility.

P A Sandstrom1, D A Chow

  • 1University of Manitoba, Department of Immunology, Winnipeg, Canada.

Carcinogenesis
|November 1, 1988
PubMed
Summary
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Phorbol ester tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) reversibly reduces tumor cell sensitivity to natural resistance mechanisms. This TPA-induced resistance aids tumor survival and progression in vivo.

Area of Science:

  • Oncology
  • Immunology
  • Carcinogenesis

Background:

  • The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) is a known tumor promoter.
  • Tumor cells must evade host immune defenses to survive and progress.

Purpose of the Study:

  • To investigate the effect of TPA on the sensitivity of murine tumor cells to natural resistance mechanisms.
  • To determine if TPA-induced changes in natural resistance correlate with tumor progression in vivo.

Main Methods:

  • Murine tumor cell lines (L5178Y-F9 and SL2-5) were cultured with TPA.
  • Sensitivity to complement-mediated lysis, natural antibodies (Nab), activated macrophages, and hypotonic lysis were assessed in vitro.
  • Tumorigenicity and metastatic potential were evaluated in syngeneic DBA/2 mice.

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Main Results:

  • TPA treatment reversibly reduced tumor cell sensitivity to natural resistance mechanisms, including Nab and NK cells.
  • TPA-treated cells showed reduced Nab binding capacity.
  • Tumorigenicity and metastatic potential increased in TPA-treated tumors in vivo.
  • Reversal of resistance occurred upon removal of TPA, indicating a requirement for continuous TPA exposure.

Conclusions:

  • TPA induces reversible reductions in tumor cell sensitivity to natural resistance.
  • These reductions may facilitate tumor survival and progression during the promotion phase of carcinogenesis.
  • TPA-induced evasion of host defenses is a crucial component of tumor promotion.