Expression pattern of sonic hedgehog and effect of topical mitomycin C on its expression in human ocular surface

Kyoko Fujita1, Takeshi Miyamoto2, Yuka Okada2

  • 1Department of Ophthalmology, Wakayama Medical University, Wakayama, Japan. kyoko@wakayama-med.ac.jp.

Abstract

Insights

Human ocular surface neoplasms show increased sonic hedgehog (Shh) expression, which is reduced by topical mitomycin C. This suggests Shh pathway modulation may contribute to the drug

Area of Science:

  • Ophthalmology
  • Oncology
  • Molecular Biology

Background:

  • The sonic hedgehog (Shh) signaling pathway plays a role in cellular development and cancer.
  • Ocular surface neoplasms, such as squamous cell carcinoma, can affect vision and eye health.

Purpose of the Study:

  • To investigate the expression of Shh in human ocular surface neoplasms.
  • To determine the effect of topical mitomycin C on Shh expression in these tumors.

Main Methods:

  • Immunohistochemical analysis of conjunctival tissues from normal subjects and patients with ocular surface neoplasms.
  • Evaluation of Shh and Patched 1 (Ptc) expression.
  • In vitro study using a cultured squamous cell carcinoma cell line to assess mitomycin C's effect on Shh expression.

Main Results:

  • Basal conjunctival epithelial cells showed faint Shh immunoreactivity.
  • Squamous cell carcinoma and ocular epithelial dysplasia cells exhibited markedly increased Shh expression.
  • Topical mitomycin C treatment significantly reduced Shh expression in ocular epithelial dysplasia and in cultured cancer cells.

Conclusions:

  • Ocular surface epithelial cells express low levels of Shh, with increased expression during malignant transformation.
  • The reduction of Shh expression by topical mitomycin C may contribute to its therapeutic effectiveness against ocular surface neoplasms.

Related Concept Videos

Hedgehog Signaling Pathway02:33

Hedgehog Signaling Pathway

The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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,...
Induced Pluripotent Stem Cells01:06

Induced Pluripotent Stem Cells

Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic cells are...
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...