Related Experiment Video

Updated: Aug 7, 2026

Spheroid Assay to Measure TGF-β-induced Invasion
09:18

Spheroid Assay to Measure TGF-β-induced Invasion

Published on: November 16, 2011

IGFBP-3 mediates TGF beta 1 proliferative response in colon cancer cells

S Kansra1, D Z Ewton, J Wang

  • 1Pathology Department, Upstate Medical University, Syracuse, New York, USA.

International Journal of Cancer
|July 18, 2000
PubMed

Insights

Insulin-like growth factor binding protein 3 (IGFBP-3) drives colon cancer cell proliferation, mediating the effects of transforming growth factor beta 1 (TGF-β1). Elevated IGFBP-3 in tumors suggests a role in cancer growth and progression.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Human tumor cells often resist growth inhibition by TGF-β1.
  • Mechanisms of resistance include mutations in TGF-β signaling pathways or retinoblastoma (Rb) gene alterations.
  • Previous studies indicated TGF-β1-induced growth stimulation in colon cancers without Rb gene deletion.

Purpose of the Study:

  • To investigate the role of insulin-like growth factor binding protein 3 (IGFBP-3) in mediating TGF-β1-induced proliferation in aggressive colon carcinoma cell lines.
  • To determine if IGFBP-3 is upregulated in colon cancer tissues and contributes to tumor growth.

Main Methods:

  • Treatment of colon carcinoma cell lines with TGF-β1.
  • Assessment of IGFBP-3 abundance following TGF-β1 treatment.
  • Inhibition of TGF-β1 effects using phosphorothiolated antisense oligonucleotides targeting IGFBP-3.
  • In vitro studies on IGFBP-3-induced carcinoma cell growth.
  • Quantification of mature IGFBP-3 levels in resected colon cancer tissues and adjacent normal tissues.

Main Results:

  • TGF-β1 treatment increased IGFBP-3 abundance in three aggressive colon carcinoma cell lines.
  • Antisense oligonucleotides to IGFBP-3 blocked the growth-promoting effects of TGF-β1.
  • IGFBP-3 demonstrated dose- and time-dependent induction of carcinoma cell growth in vitro.
  • Mature IGFBP-3 levels were elevated at least twofold in 70% of resected colon cancers compared to normal adjacent tissue.

Conclusions:

  • IGFBP-3 mediates TGF-β1-induced proliferation in aggressive colon carcinoma cells.
  • IGFBP-3 plays a significant role in promoting colon cancer cell growth.
  • Elevated IGFBP-3 levels in colon tumors suggest it confers a selective growth advantage in vivo.

More Related Videos

Isolation of Primary Myofibroblasts from Mouse and Human Colon Tissue06:59

Isolation of Primary Myofibroblasts from Mouse and Human Colon Tissue

Published on: October 12, 2013

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Related Concept Videos

TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

Role Of Notch Signalling In Intestinal Stem Cell Renewal

Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Inflammatory Bowel Disease II: Ulcerative Colitis01:20

Inflammatory Bowel Disease II: Ulcerative Colitis

Ulcerative colitis is a chronic inflammatory disorder of the colon characterized by continuous mucosal inflammation that typically begins in the rectum and extends proximally in a uniform pattern. Its pathogenesis involves a complex interplay of genetic predisposition, immune dysregulation, and environmental influences. These factors converge to impair the colon’s epithelial defenses and promote an exaggerated inflammatory response against luminal contents.Breakdown of the Mucosal BarrierA...
Inflammatory Bowel Disease III: Crohn's Disease01:25

Inflammatory Bowel Disease III: Crohn's Disease

Crohn’s disease is a chronic, relapsing form of inflammatory bowel disease characterized by segmental, transmural inflammation that can affect any part of the gastrointestinal tract. Its pathogenesis arises from a combination of genetic susceptibility, environmental exposures, epithelial barrier dysfunction, and immune dysregulation. Together, these factors lead to an exaggerated immune response against components of the gut microbiome.Genetic and Environmental InfluencesMultiple genetic...