Accession Number:

ADA609025

Title:

The Role of Megakaryocytes in Breast Cancer Metastasis to Bone

Descriptive Note:

Final rept. 15 Apr 2010-14 Apr 2014

Corporate Author:

PENNSYLVANIA STATE UNIV STATE COLLEGE

Personal Author(s):

Report Date:

2014-05-01

Pagination or Media Count:

24.0

Abstract:

Hypothesis megakaryocytes MKs contribute to the growth of metastatic breast cancer in the bone either by preparing a niche andor by responding to the cytokines of the marrow resulting from the interaction of the cancer with cells of the marrow. We found that MKs increased in the femurs of mice bearing MDA-MB-231 human cancer. We compared MKs in femurs of nude mice inoculated with cancer cells into the mammary gland non-metastasizing with intracardiac injection bone metastasizing. Immunohistochemistry and counting of vonWillibrand factor, multinucleated cells were used to determine MK numbers. Blood platelets, serum levels of thrombopoietin TPO and SDF-1 were measured. In another model, mouse mammary tumor cells 4T1.2 metastaic or 67NR, non-metastatic were injected into the mammary glands, and femurs and spleens assayed over time. The MK increased only in the metastatic model suggesting that the effect was local to the bone. However, the increase of MK was greatest in the spleen, extramedullary hematopoiesis. Results of an in vitro complementary study indicated that both osteoblasts and breast cancer cells together produced factors that increase MK differentiation. In the meantime TPO-- mouse embryos were regenerated and mice were backcrossed to Balbc so that metastasis could be determined in MK deficient mice. The TPO-- mice appear to be more susceptible to metastasis than the wildtype, with metastese appearing more quickly and spreading further after inoculation.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE