SCIENTIFIC REPORT 2004 - Sylvester Comprehensive Cancer Center

T U M O R C E L L B I O L O G Y P R O G R A M
ELIZABETH J. FRANZMANN, M.D.
Assistant Professor of Otolaryngology
DESCRIPTION OF RESEARCH
Dr. Franzmann 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, successful treatment
of head and neck cancer only occurs 50
percent 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 health care costs.
Screening and staging methods for HNSCC also
are deficient.
To better understand the molecular mechanisms
that lead to HNSCC, Dr. Franzmann’s
laboratory is investigating the CD44 family of
alternatively spliced isoforms. Some CD44
isoforms are found normally in cells. Other
isoforms termed CD44 variant (CD44v) isoforms
are found in tumor tissues and are associated with
poor prognosis. There is particular interest in the
CD44v3-containing isoforms since these
isoforms contain a growth factor binding site.
Preliminary work suggests that CD44v3-containing
isoforms are differentially expressed in
HNSCC tumors and normal tissue and may be
involved in tumor cell growth. Using reverse
transcriptase-polymerase chain reaction (RT-
PCR), southern blot, cloning, and sequencing,
the laboratory is defining CD44v3-containing
isoform expression in head and neck tumor and
normal tissues. The laboratory will perform immunohistochemical
staining to characterize
CD44v3 expression at the protein level. Transfection
studies will be used to investigate the mechanisms
by which these isoforms alter HNSCC cell
behavior. In addition to identifying HNSCC in
the early stage when treatment is much more effective,
Dr. Franzmann’s laboratory is evaluating
whether a salivary CD44 ELISA test is a useful
screening tool for HNSCC.
SELECTED PUBLICATIONS
2003
Franzmann, EJ, Schroeder, GL, Goodwin, WJ,
Weed, DT, Fisher, P, and Lokeshwar, VB. Expression
of tumor markers hyaluronic acid and hyaluronidase
(HYAL1) in head and neck tumors.
International Journal of Cancer 106:438-45, 2003.
HIGHLIGHTS/DISCOVERIES
• CD44v3-containing isoforms are found in
HNSCC tumor tissues and cell lines using RT-
PCR. CD44v3 and CD44v3-10 have been
cloned and sequenced from HNSCC cell lines.
• In a preliminary study including 26 patients
with HNSCC and ten normal controls, CD44
levels were significantly higher in HNSCC patient
saliva compared to normal volunteer saliva.
ZHIYONG HAN, PH.D.
Assistant Professor of Biology
DESCRIPTION OF RESEARCH
Dr. Han’s research seeks to understand how
anti-cancer drugs induce apoptosis of cancer
cells. His recent work focuses on how the natural
product camptothecin (CPT) and its semi-synthetic
derivatives such as CPT-11, 9-amino-CPT
(9AC), and 9-nitro-CPT (9NC) induce apoptosis
of human colon cancer cells.
CPT and its derivatives are considered important
anti-cancer drugs. Many aspects of the
mechanism by which these drugs exert their
death effect on cancer cells, however, remain
largely unknown. In recent years, Dr. Han and
his colleagues have used a cell model of human
colon cancer to demonstrate that treatment with
low doses of CPT induces senescence in the presence
of a protein called p21, but apoptosis in the
absence of p21. Therefore, p21 is a key determinant
of the outcome of colon cancer cells treated
with CPT drugs at doses that are relevant to
clinical application. CPT treatment of colon cancer
cells with p21 should result in disease stabili-
UM/Sylvester Comprehensive Cancer Center Scientific Report 2004 75