THE ROLE OF A BONE MORPHOGENETIC PROTEIN IN LUNG CANCER

Project Details

Description

DESCRIPTION (provided by applicant): Lung cancer remains a devastating
disease with the majority of patients developing distant metastasis. To
identify genes that may regulate metastasis, we used representational
differential analysis (RDA) to identify genes highly expressed in human lung
carcinomas. RDA identified bone morphogenetic protein 2 (BMP-2) expression in
lung cancer and subsequent studies showed BMP-2 is highly expressed in the
majority of lung cancers with low levels of expression in normal lung tissue.
We show that the inhibition of BMP-2 activity of the A549 lung cancer cell
line injected into nude mice causes a significant decrease in tumor growth.
We hypothesize that the mechanism(s) by which BMP-2 promotes the development
of tumor growth occurs through stimulation of angiogenesis and production of
growth promoting cytokines. We will test this hypothesis by performing the
following studies. (1) To analyze BMP-2 regulation of angiogenesis, lung
cancer cell lines will be co-injected into nude mice with Affi-blue agarose
beads coated with albumin, recombinant BMP-2, or the BMP-2 antagonist, noggin.
Differences in vessel cooption, regression, and proliferation will be assessed
in developing tumors using immunohistochemistry. To determine the mechanism
by which BMP-2 stimulates angiogenesis by assessing both the regulation of
vascular endothelial growth factor (VEGF) and activation of BMP-2 specific
receptors. Cell lines transfected with dominant negative BMP receptors will
be used to determine which BMP receptor is activated to induce angiogenesis.
(2) To examine the paracrine and autocrine regulation of BMP-2 on known growth
promoting cytokines and assess the role of the identified cytokine in
promoting bmp-2 stimulation of tumor growth and angiogenesis. (3) To examine
in patient derived tissue samples whether the level of BMP-2 ligand and
receptor expression in primary and metastatic lung tumors correlates with
vascular invasion, tumor grade, cell differentiation, monocyte infiltration,
and the frequency of distant metastatic spread. Our long-term goal is to use
BMP-2 inhibiting therapy as a modality to prevent the progression of lung
cancer.
StatusFinished
Effective start/end date7/8/026/30/05

Funding

  • National Cancer Institute: $156,870.00
  • National Cancer Institute: $156,870.00
  • National Cancer Institute: $156,870.00

ASJC

  • Oncology
  • Cancer Research

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