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Title: Expression of gastrin precursors by CD133-positive colorectal cancer cells is crucial for tumour growth.
Austin Authors: Ferrand, Audrey;Sandrin, Mauro S ;Shulkes, Arthur;Baldwin, Graham S
Affiliation: Department of Surgery, Austin Health, University of Melbourne, Heidelberg 3084, Victoria, Australia
Issue Date: 15-Jan-2009
Publication information: Biochimica Et Biophysica Acta 2009; 1793(3): 477-88
Abstract: Precursors of the hormone gastrin, progastrin and glycine-extended gastrin (G-gly), have been detected in colorectal polyps and tumours, and in the blood of patients with colorectal cancer (CRC), while their expression is lower in healthy subjects. The surface glycoproteins CD133 and CD44 have been identified as possible markers for CRC stem cells. Our aims were to investigate whether progastrin and G-gly are expressed by CD133-positive cells in human CRC tissues and in the human CRC cell line DLD-1, and to determine whether this expression is biologically relevant. The great majority of the cells expressing CD133 also expressed gastrin precursors in both DLD-1 cells, which retain a stem cell-like subpopulation, and human CRC specimens. The CD133high/CD44high/progastrinhigh cells gave rise to larger tumours in SCID mice compared to CD133low/CD44low/progastrinlow cells. The CD133high/CD44high/progastrinhigh cells displayed enhanced activation of the signalling molecules JAK2, STAT3, ERK1/2 and Akt, known to regulate the induction of proliferation and/or survival by gastrin precursors. Moreover, downregulation of the gastrin gene in DLD-1 cells reduced the expression of cancer stem cell markers and abolished tumour development in SCID mice. We conclude that gastrin precursors may provide a target for therapies directed against the cells responsible for tumour development and recurrence.
Gov't Doc #: 19321126
DOI: 10.1016/j.bbamcr.2009.01.004
Journal: Biochimica et biophysica acta
Type: Journal Article
Subjects: Animals
Antigens, CD.metabolism
Antigens, CD44.metabolism
Antigens, Neoplasm.metabolism
Cell Line, Tumor
Colorectal Neoplasms.genetics.metabolism
Flow Cytometry
Mice, SCID
Protein Precursors.genetics.metabolism
Receptors, G-Protein-Coupled.metabolism
Signal Transduction
Tumor Markers, Biological.metabolism
Appears in Collections:Journal articles

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