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Non-Small Cell Lung Cancer

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Trial Information

CD44 is a cell surface receptor for the extracellular matrix hyaluronan. It mediates
adhesion of cells to the extracellular matrix. Its ability to organize extracellular matrix
into a medium is also used by cancer cells in their becoming metastatic. Invasive tumor
cells are frequently observed to bind hyaluronate.

CD44 gene is made up of 20 exons, at least 10 of which are variably expressed due to
alternative splicing of the mRNA. The standard form, CD44s, has a coding sequence of exons
1-5 and 16-20. Variant isoforms (CD44v), all larger, arise from alternative splicing of
combinations of exons 6-15 (v1-10). A variant isoform CD44 can induce metastasis of a rat
pancreatic carcinoma. Studies in human tumors, however, have produced variable results. Some
breast cancers demonstrate positive correlation between CD44v expression and tumor
progression, while others lack any correlation. Some colorectal tumors even show an inverse
correlation. CD44 has also been demonstrated to be a metastasis suppressor gene for prostate
cancer. Thus, CD44 may be a marker for metastasis for some tumors, but not for others, and
it may actually be a metastasis suppressor gene for yet another groups of tumors.

For primary lung cancer, the correlation between CD44 expression and tumor metastasis has
not been established. The metastasis-prone small cell lung cancer rarely showed any
immunohistochemical staining for CD44s or CD44v. For non-small cell lung cancer (NSCLC),
some studies showed positive correlation between immunohistochemical CD44v expression and
tumor progression, while others showed no correlation. Our own study using RT-PCR,
sequencing and immunohistochemical staining showed that in pulmonary adenocarcinoma, CD44v6
expression is down-regulated as the disease progressed. Based on our finding, and the
observation that CD44s and CD44v expression are low in metastasis-prone small cell lung
cancer, we assue that CD44 is a metastasis suppressor gene which is inactivated in lung
cancers. Because in prostate cancer DNA hypermethylation has been shown to be related to the
down-regulation of CD44 gene, we plan to study the methylation status of the transcriptional
regulatory region of CD44 gene in primary lung cancer. We’ll study CD44 expression by
immunohistochemistry, the methylation status of CD44 regulatory region by sequencing of the
bisulfite-modified genomic DNA, and correlate these two findings with each other, and with
histologic type, tumor staging and survival.

Inclusion Criteria:

- Non-small cell lung cancer

Exclusion Criteria:

- No

Type of Study:


Study Design:

Observational Model: Defined Population, Observational Model: Natural History, Time Perspective: Longitudinal, Time Perspective: Retrospective

Principal Investigator


Investigator Role:

Principal Investigator

Investigator Affiliation:

Department of Labrotoary Medicine, National Taiwan University Hospital Taipei


Taiwan: Department of Health

Study ID:




Start Date:

August 2005

Completion Date:

Related Keywords:

  • Non-Small Cell Lung Cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms