Related Experiment Video
Updated: Jun 25, 2026
Real-time Imaging of Myeloid Cells Dynamics in ApcMin/+ Intestinal Tumors by Spinning Disk Confocal Microscopy
Published on: October 6, 2014
Deficiency of SPARC suppresses intestinal tumorigenesis in APCMin/+ mice
Owen J Sansom1, Fiona C Mansergh, Martin J Evans
1Beatson Institute of Cancer Research, Glasgow, Scotland, UK. o.sansom@beaston.gla.ac.uk
Background And Aims:
SPARC (secreted protein acidic, rich in cysteine) is a matricellular protein that has been found to be activated in a number of human cancers. More recently, it has been shown to be upregulated in human gastric and colorectal cancer. We therefore wished to address the functional importance of SPARC upregulation to intestinal tumorigenesis in vivo.
Methods:
SPARC upregulation was determined in intestinal adenomas of tumour-prone Apc(Min/+) mice at both the RNA and the protein level. To determine the functional importance of SPARC for intestinal tumorigenesis we then intercrossed Sparc knockout mice with Apc(Min/+) mice (n = 20). Intestinal enterocyte migration was examined using bromodeoxyuridine labelling studies.
Results:
Levels of murine Sparc and several related proteins were upregulated in adenomas arising in Apc(Min/+) mice. A deficiency of Sparc strongly suppressed adenoma formation in Apc(Min/+) mice (p>or=0.0001). Importantly, a deficiency of Sparc also accelerated enterocyte migration (p = 0.01), as perturbed slow epithelial migration may underpin adenoma formation in the intestine.
Conclusions:
These data implicate Sparc in both cell migration and tumour formation, and identify Sparc as a potential therapeutic target for colorectal cancer.
Insights
Secreted protein acidic, rich in cysteine (SPARC) promotes intestinal tumor formation and hinders cell migration. SPARC deficiency suppresses adenoma development, suggesting it is a therapeutic target for colorectal cancer.
Area of Science:
- Oncology
- Cell Biology
- Gastroenterology
Background:
- Secreted protein acidic, rich in cysteine (SPARC) is a matricellular protein implicated in human cancers.
- SPARC has been observed to be upregulated in gastric and colorectal cancers.
- Its functional significance in intestinal tumorigenesis warrants investigation.
Purpose of the Study:
- To investigate the role of SPARC upregulation in intestinal tumorigenesis in vivo.
- To determine the functional importance of SPARC in the development of intestinal tumors.
Main Methods:
- SPARC upregulation was quantified in intestinal adenomas of Apc(Min/+) mice at RNA and protein levels.
- Sparc knockout mice were crossed with Apc(Min/+) mice to assess SPARC deficiency effects.
- Bromodeoxyuridine labeling was used to examine intestinal enterocyte migration.
Main Results:
- SPARC and related proteins were upregulated in Apc(Min/+) mouse adenomas.
- SPARC deficiency significantly suppressed adenoma formation in Apc(Min/+) mice (p≥0.0001).
- SPARC deficiency accelerated enterocyte migration (p=0.01), suggesting a role in epithelial dynamics.
Conclusions:
- SPARC is implicated in both cell migration and tumor formation.
- SPARC deficiency suppresses intestinal adenoma formation.
- SPARC represents a potential therapeutic target for colorectal cancer treatment.
Related Concept Videos
02:23Abnormal Proliferation
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
01:23Renewal of Intestinal Stem Cells
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
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...