ENDOGENOUS OPIOID MODULATION OF HUMAN PANCREATIC CANCER

Project: Research project

Project Details

Description

Pancreatic cancer is the 4th leading cause of cancer-related deaths in
the U.S. Little is known about the origin, pathogenesis, or treatment of
this neoplasia. The opioid growth factor (OGF), [Met5]-enkephalin, is a
native inhibitory peptide that is particularly targeted to cell
proliferative events. The repressive activity of OGF on cell growth is
mediated by the zeta opioid receptor. CCF is a negative growth factor in
pancreatic cancer both in vitro and in vivo, Blockade of OGF action by
the potent opioid antagonist naltrexone increases pancreatic cancer cell
proliferation, indicating the tonic activity of OGF. Both OGF and zeta
receptor are in pancreatic tumor cells. This grant hypothesizes that a
native opioid peptide inhibits the growth of human pancreatic cancer, and
does so through a unique opioid receptor. To test this hypothesis, we
propose to: (l) Examine the cellular mechanisms of endogenous opioid
action on human pancreatic tumor cell function, including DNA synthesis
and the cell cycle. (2) Investigate the autocrine production of the
opioid peptide related to growth of human pancreatic cancer. (3) Define
the regulatory properties of opioid peptide-receptor interaction with
respect to human pancreatic cancer cells. (4) Clone and sequence the
zeta opioid receptor in human pancreatic neoplasia, and elucidate the
function of this receptor using overexpression studies. (5) Learn about
the mechanisms of endogenous opioid activity with regard to the incidence
and growth of human pancreatic tumors from xenografts in nude mice. These
studies will contribute to comprehending the biology of human cancer, and
may provide clues to strategies for the treatment of pancreatic
neoplasia. Information derived from the proposed investigation would be
the first to identify a natural inhibitory substance and its receptor
that serve to regulate pancreatic cancer. This research is part of a
long-range program in cellular and molecular oncology which seeks to
define the fundamental principles underlying pancreatic cancer in humans.
StatusFinished
Effective start/end date12/23/9611/30/97

Funding

  • National Cancer Institute

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