SPARC is expressed in human uveal melanoma and its abrogation reduces tumor cell proliferation

Shawn C Maloney1, Jean-Claude Marshall, Emilia Antecka

  • 1The Henry C. Witelson Ocular Pathology Laboratory, McGill University, Montreal, QC, H3A 2B4, Canada. shawn.maloney@mail.mcgill.ca

Anticancer Research
|August 8, 2009
PubMed
Abstract

Insights

Secreted protein acidic and rich in cysteine (SPARC) is highly expressed in uveal melanoma (UM). Inhibiting SPARC significantly reduced UM cell proliferation, suggesting it is a potential therapeutic target for this eye cancer.

Area of Science:

  • Oncology
  • Ophthalmology
  • Molecular Biology

Background:

  • Secreted protein acidic and rich in cysteine (SPARC) is implicated in various cancer progressions.
  • Uveal melanoma (UM) is a primary intraocular malignancy.
  • The role of SPARC in UM pathogenesis requires further investigation.

Purpose of the Study:

  • To investigate the expression levels of SPARC in uveal melanoma.
  • To determine the functional role of SPARC in UM cell proliferation.
  • To evaluate SPARC as a potential therapeutic target for UM.

Main Methods:

  • SPARC expression was analyzed in UM cell lines and human UM tissues using RT-PCR and immunocytochemistry.
  • UM cell lines were transfected with SPARC-targeting small interfering RNA (siRNA).
  • Proliferation assays were performed on transfected cell lines and in a rabbit xenograft model.

Main Results:

  • SPARC siRNA transfection led to a significant reduction in UM cell proliferation compared to control groups.
  • All examined human UM cases showed positive SPARC staining.
  • SPARC was also expressed in primary and metastatic tumors from a rabbit xenograft model.

Conclusions:

  • SPARC is highly expressed in uveal melanoma.
  • SPARC plays a role in promoting UM cell growth.
  • Targeting SPARC may offer a novel therapeutic strategy for inhibiting UM progression.

Related Concept Videos

Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The Retinoblastoma Gene01:20

The Retinoblastoma Gene

Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Tumor Progression02:07

Tumor Progression

Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...