Research Knowledgebase
Description of Research
Dr. Franzmann's lab is interested in the molecular mechanisms of head and neck squamous cell cancer (HNSCC) progression. Despite rigorous therapy using various combinations of surgery, radiation and chemotherapy as initial treatment of HNSCC is successful only 50% of the time. Because of the complexity of the head and neck, current therapy often results in facial disfigurement, speech and swallowing problems and substantial healthcare costs. Certain groups, including blacks and the economically disadvantaged, suffer disproportionately from this disease. Improved screening and staging methods for HNSCC are needed.
This lab is investigating a simple, inexpensive early detection method for HNSCC. Data on over 180 subjects suggests that the soluble form of CD44, an adhesion molecule involved in tumorigenesis, is elevated in oral rinses of HNSCC patients compared to controls, and distinguishes HNSCC from noncancer with 62-79% sensitivity and 88-100% specificity. Further pilot work, in collaboration with Dr. Vinata Lokeshwar, suggests that two related tumor markers, hyaluronic acid and hylaronidase, are also detectable in oral rinses, and when combined with the solCD44 test result in a highly sensitive and specific test for HNSCC. Since the test uses oral rinses and simple ELISA or ELISA-like assays, it is very easy to administer, noninvasive and inexpensive. Such qualities are very important for populations with limited access to expert care. Our study includes subjects enrolled from an underserved clinic, rich in minorities, which will allow us to confirm whether this test is useful in the population that needs it the most.
The laboratory is also working to understand the role CD44 plays in HNSCC tumorigenesis. They are particularly interested in the CD44v3-containing isoforms, since these isoforms contain a growth factor binding site. Using quantitative PCR, cloning and sequencing, and transfection experiments, preliminary work suggests that CD44v3-containing isoforms are differentially expressed in HNSCC tumors and normal tissue and may be involved in tumor cell migration. Using similar techniques, they have also shown another isoform CD44s, which is the main isoform expressed in oral rinses, also appears to be involved in HNSCC growth and migration.
Highlights/Discoveries
- Levels of soluble CD44 are significantly elevated in oral rinses from HNSCC patients compared to subjects without cancer and may be useful for early detection of HNSCC.
- A pilot study with Dr. Singal’s group showed that subjects with low solCD44 levels had hypermethylation of the CD44 promoter which is known to turn the gene off. Since none of the control samples were methylated, including methylation status of the CD44 gene may further improve sensitivity of the early detection test.
- Have shown that CD44v3, an alternatively spliced isoform of CD44 that contains a growth factor binding domain, is overexpressed at the transcript level in HNSCC tissues compared to control tissues. Overexpression of the CD44v3 isoform in a HNSCC cell line is associated with increased cell migration.
Selected Cancer-Related Publications
Germani RM, Civantos FJ, Elgart G, Roberts B, Franzmann EJ. Molecular markers of micrometastasis in oral cavity carcinomas. Otolaryngol Head Neck Surg 141:52-8, 2009. PubMed link
Goodwin WJ, Thomas GR, Parker DF, Joseph D, Levis S, Franzmann E, Anello C, Hu JJ. Unequal burden of head and neck cancer in the United States. Head Neck 30:358-71, 2008. PubMed link
Sargi ZB, Franzmann EJ. Elective neck dissection in early-stage oral squamous cell carcinoma. Head Neck 30:273-4, 2008. PubMed link
Franzmann EJ, Reategui EP, Pedros F, Pernas FG, Karakullukcu BM, Carraway K,Hamilton K, Singal R, Goodwin WJ. Soluble CD44 is a Potential Marker for the Early Detection of Head and Neck Cancer. Cancer Epidemiol Biomarkers Prev;16(7):1348-55,2007. PubMed link
For full description of Multidisciplinary Research Program(s), Cancer Epidemiology & Prevention Program.
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