Accession Number : ADA550794


Title :   A New In Vitro Model of Breast Cancer Metastasis to Bone


Descriptive Note : Annual rept. 15 Mar 2008-14 Mar 2009


Corporate Author : PENNSYLVANIA STATE UNIV UNIVERSITY PARK


Personal Author(s) : Mastro, Andrea M ; Vogler, Erwin A ; Gay, Carol V


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a550794.pdf


Report Date : Apr 2009


Pagination or Media Count : 159


Abstract : Breast cancer frequently metastasizes to the bone where it disrupts the balance between osteoblasts and osteoclasts and leads to osteolytic degradation. The objective of this study was to test the hypothesis that osteolytic bone metastases results partly from the effect of the cancer cells on the osteoblasts, i.e., the cancer cells prevent osteoblasts from accreting mineralized tissue, ultimately leading to accelerated skeletal degradation. To test this idea, we proposed to develop an existing three-dimensional culture system into an in vitro test system for studying the interactions between osteoblasts and metastatic breast cancer cells. The objectives were to characterize the morphology and physiology of osteoblasts (MC3T3-E1) cultured as a 3D osteoid in a bioreactor and determine how they reacted to the presence of human metastatic breast cancer cells (MDA-MB-231). In addition, we proposed to determine how this interaction was affected by changing the oxidative state of the microenvironment with selenium supplementation. We also used this system to determine how the currently used drugs, zoledronic acid and doxetaxel, affected osteoblasts and cancer cells in the 3D model. Osteoblasts (OB) grew into bone-like tissue in a 3D model system. Pre-OB matured to OB and eventually to osteocyte-like cells. These cells met the criteria of osteocytes based on shape and protein expression. In addition, the density was similar to that reported for calvaria bone. The 3-D system was used to examine the interaction of metastatic breast cancer cells, MDA-MB-231, with OB. The cancer cells brought about profound effects on the osteoid tissue. The OB changed from cuboidal to spindle shape. The cancer cells aligned into an Indian filing pattern, and penetrated the osteoid. Using RT-PCR, we found that cancer cells downregulated OB differentiation proteins but increased inflammatory cytokines.


Descriptors :   *BONES , *BREAST CANCER , *CELLS(BIOLOGY) , *IN VITRO ANALYSIS , *METASTASIS , *MODELS , *OSTEOLYSIS , DEGRADATION , INTERACTIONS , MORPHOLOGY , PHYSIOLOGY , SELENIUM , THREE DIMENSIONAL


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE