X-linked dominant growth suppression of transplanted tumors in C57BL/6J-scid mice

Mark Wood1, Taturo Udagawa, Yasuhiro Hida

  • 1Vascular Biology Program and Department of Surgery, Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts 02115, USA.

Cancer Research
|July 5, 2005
PubMed

Insights

Tumor growth varies by mouse strain. C57BL/6J-scid mice show suppressed tumor growth, linked to a dominant gene on the X chromosome, impacting xenograft development.

Area of Science:

  • Immunology
  • Genetics
  • Oncology

Background:

  • Host factors significantly influence tumor xenograft growth rates.
  • Genetic background of mice, including immune status, plays a critical role in tumor susceptibility.
  • Severe combined immunodeficient (SCID) mice are commonly used for xenograft studies, but strain-specific differences exist.

Purpose of the Study:

  • To investigate the differential growth rates of tumor xenografts in distinct mouse strains.
  • To determine the genetic basis for the observed variations in tumor growth suppression.
  • To identify the specific genetic elements responsible for host-mediated tumor growth control.

Main Methods:

  • Tumor xenografts were implanted into three genetically distinct SCID mouse strains: C.B-17-scid, C57BL/6J-scid, and C3H-scid.
  • Bone marrow transplantation was performed from C57BL/6J-scid to C.B-17-scid mice to assess immune-mediated effects.
  • Reciprocal crosses between C.B-17-scid and C57BL/6J-scid mice were conducted to analyze inheritance patterns of tumor growth phenotypes.

Main Results:

  • Tumor xenografts exhibited significantly reduced growth rates in C57BL/6J-scid mice compared to other strains.
  • Bone marrow transplantation did not transfer the slow-growing phenotype, suggesting a non-immune mechanism.
  • Reciprocal crosses revealed that tumor growth suppression is X-linked and influenced by the paternal C.B-17-scid strain in male progeny, while C57BL/6J-scid males showed fast growth.
  • A dominant allele on the X chromosome of C57BL/6J mice was identified as responsible for suppressing tumor growth.

Conclusions:

  • Significant strain-dependent variations exist in the capacity of mice to support tumor xenograft growth.
  • Host genetic factors, specifically a dominant allele on the X chromosome of C57BL/6J mice, play a crucial role in suppressing tumor growth.
  • These findings highlight the importance of considering host genetics in xenograft models for cancer research and drug development.