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P3.71. CD147 expression patterns in two distinct orthotopic mouse models of head and neck squamous cell carcinomas (HNSCC)
P3.71. CD147 expression patterns in two distinct orthotopic mouse models of head and neck squamous cell carcinomas (HNSCC) J. Wu a, M.W. Lingen b, N. Vigneswaran a,* a Department of Diagnostic Sciences, The University of Texas Dental Branch at Houston, United States b Department of Pathology, University of Chicago Medical Center, United States
Introduction: CD147 mediates tumour-microenvironment interactions and thereby promotes tumour progression, resistance to chemotherapy and maintenance of cancer stem cell niche. We showed that CD147 upregulation occurs at a very early stage of human HNSCC tumorigenesis which is mediated by EGFR activation. Recent reports suggest that CD147 targeted therapy may enhance the antitumor efficacy of chemotherapeutic drugs. Hence, preclinical HNSCC animal modes closely mimicking early and advanced stages of human HNSCC are needed to test CD147 targeted therapies. Objective: To describe the CD147 expression patterns in two distinct types of immunocompetent HNSCC mouse models. Methods: CBA mice tongue carcinogenesis model was established by treating these mice with 4-NQO (100 lg/ml) in drinking water for 16–24 weeks. CD147 expression in normal tongue mucosae (n = 4), tongue mucosal hyperplasias (n = 4), dysplasias (n = 5) and invasive squamous cell carcinomas were examined immunohistochemically. To develop murine isograft HNSCC model, we implanted murine SCC cell line LY2 into the mandibular buccal sulcus of syngeneic BALB/c mice. Expression pattern of CD147 was examined immunohistochemically in the primary and metastatic LY2 tumours harvested from the BALB/c mice. Results: Only the basal cells of normal tongue mucosae in both CBA and BALB/c mice were positive for CD147. CD147 overexpression was noted in all 4NQO-induced dysplastic and invasive SCC cells of CBA mice. Implantation of LY2 cells formed tumours in 100% of the mice and these tumours grow rapidly and produced regional lymph node (90%) and distant lung metastases (35%). CD147 immunohistochemistry revealed overexpression of CD147 in both primary and metastatic tumours of this tumour model.Conclusion: The 4NQO induced tongue precancers and cancers in CBA mice recapitulate early-stage human HNSCC development both in histopathology and CD147 expression patterns. The orthotopic isograft mouse model of HNSCC closely simulates a high-grade human HNSCC in its histology, CD147 expression pattern and which positively biologic behaviour. doi:10.1016/j.oos.2009.06.597
P3.72. KLK4 expression and functions in oral cancer P. Papagerakis a, Y. Yamakoshi a, J. Simmer a, G. Pannone b, S. Papagerakis a,* a b
University of Michigan, United States University of Foggia, Italy
Background: Kallikrein-related-peptidase-4 (KLK4) is a trypsin fold serine protease from the 15-member human KLK family. KLK4 was discovered by scientists of the dental enamel field being the major protease that catalyzes the degradation of proteins in the enamel extra-cellular matrix allowing enamel to achieve its extremely high degree of mineralization. Since then, several macromolecular substrates of potential patho-physiological relevance have been identified, including another KLK family member, pro-prostate-specific antigen (also known as KLK3), the pro-urokinase-type plasminogen
225
activator, the fibrinogen and the urokinase-type plasminogen activator receptor. It has also been suggested that KLK4 may initiate intracellular signalling via members of the protease-activated receptor (PAR) family of G protein-coupled receptors. Studies have also associated KLK4 expression with cancer progression suggesting that KLK4’s aggressive proteolytic activity could promote tissue invasion and metastasis. Aim: To evaluate the expression and potential roles of KLK4 in oral squamous cell carcinomas (OSCC). Materials and methods: KLK4 expression was detected by immunohistochemistry, Western blots and zymograms in OSCC cell lines and tumour specimen. Proliferation, invasion, and flow adhesion assays were undertaken using high versus low/undetectable KLK4-expressing OSCC cell lines. Inhibition of KLK4 expression by siRNA was performed to investigate KLK4 roles in OSCC pathogenesis and disease progression. Results: KLK4 expression was differentially expressed in OCSS cell lines and tumour specimen. OSCC cell lines with high invasive and metastatic potential showed the highest levels of KLK4 expression. KLK4 RNA and protein expression was correlated with enzyme activity detected by zymograms. Inhibition of KLK4 expression resulted in diminished invasive and metastatic potential in OSCC cell lines. Consistently, KLK4 expression was stronger in primary OSCC specimens of patients that later developed metastases. Discussion: KLK4 is preferentially expressed in aggressive OSCC cells and might be a novel prognostic tool of OSCC disease outcome and a potential therapeutic target for OSCC treatment. doi:10.1016/j.oos.2009.06.598
P3.73. Evaluation of different oral functions following prosthodontic therapy in cleft patients I. Gitt *, T. Reiber Clinic for Prosthodontics, Dental Materials and Special Care Dentistry, University of Leipzig, Germany Introduction: In Europe clefts belong to the most frequent human malformations with a rate of 1:500 newborns. Beside the primary organic defects appear secondary disorders of speech, chewing and esthetics, which can cause psychosocial disturbances. Prosthodontic treatment is the end of the pre treatment during the first life decades with the aim of restoration the disturbed functions. With this study we examined the importance of different functions in reconstruction of the orofacial system for the patients. Methods: In cooperation with the Univ. Dept of Psychology a questionnaire was elaborated giving us the possibility of anonymity for the 28 patients (22 male, 6 female, mean age 52.1 years).This was followed by a data analysis (biography, patients data, satisfaction with prosthodontic treatment, valuation of importance of the denture for restoration of such functions like speech, chewing, esthetics, satisfaction with the present appearance, present familiar and professional job situation, getting on with the malformation and acceptance by the surrounding. The results were examined statistically. Results: Following treatment the speech function was ‘‘very important” for 68% of the patients, chewing for 57%, esthetical function for 14%. There was a significant correlation between ‘‘age and education” and importance of the esthetic function. Discussion: Resulting from these results we can state, that in this special patientgroup the speech function as mediator for interhuman relations plays the most important role in restoration of the orofacial system by dentures. Only so it is possible to realise a complete social integration for these patients.
Poster Abstracts Oral AbstractsPoster ListOrals ListPan. Disc. & Symp. Abs.Keynote Abs.Keynote Bios.ProgramIAOOWelcomeCommittee Listings
Poster session III / Oral Oncology Supplement 3 (2009) 201–236
Introduction: CD147 mediates tumour-microenvironment interactions and thereby promotes tumour progression, resistance to chemotherapy and maintenance of cancer stem cell niche. We showed that CD147 upregulation occurs at a very early stage of human HNSCC tumorigenesis which is mediated by EGFR activation. Recent reports suggest that CD147 targeted therapy may enhance the antitumor efficacy of chemotherapeutic drugs. Hence, preclinical HNSCC animal modes closely mimicking early and advanced stages of human HNSCC are needed to test CD147 targeted therapies. Objective: To describe the CD147 expression patterns in two distinct types of immunocompetent HNSCC mouse models. Methods: CBA mice tongue carcinogenesis model was established by treating these mice with 4-NQO (100 lg/ml) in drinking water for 16–24 weeks. CD147 expression in normal tongue mucosae (n = 4), tongue mucosal hyperplasias (n = 4), dysplasias (n = 5) and invasive squamous cell carcinomas were examined immunohistochemically. To develop murine isograft HNSCC model, we implanted murine SCC cell line LY2 into the mandibular buccal sulcus of syngeneic BALB/c mice. Expression pattern of CD147 was examined immunohistochemically in the primary and metastatic LY2 tumours harvested from the BALB/c mice. Results: Only the basal cells of normal tongue mucosae in both CBA and BALB/c mice were positive for CD147. CD147 overexpression was noted in all 4NQO-induced dysplastic and invasive SCC cells of CBA mice. Implantation of LY2 cells formed tumours in 100% of the mice and these tumours grow rapidly and produced regional lymph node (90%) and distant lung metastases (35%). CD147 immunohistochemistry revealed overexpression of CD147 in both primary and metastatic tumours of this tumour model.Conclusion: The 4NQO induced tongue precancers and cancers in CBA mice recapitulate early-stage human HNSCC development both in histopathology and CD147 expression patterns. The orthotopic isograft mouse model of HNSCC closely simulates a high-grade human HNSCC in its histology, CD147 expression pattern and which positively biologic behaviour. doi:10.1016/j.oos.2009.06.597
P3.72. KLK4 expression and functions in oral cancer P. Papagerakis a, Y. Yamakoshi a, J. Simmer a, G. Pannone b, S. Papagerakis a,* a b
University of Michigan, United States University of Foggia, Italy
Background: Kallikrein-related-peptidase-4 (KLK4) is a trypsin fold serine protease from the 15-member human KLK family. KLK4 was discovered by scientists of the dental enamel field being the major protease that catalyzes the degradation of proteins in the enamel extra-cellular matrix allowing enamel to achieve its extremely high degree of mineralization. Since then, several macromolecular substrates of potential patho-physiological relevance have been identified, including another KLK family member, pro-prostate-specific antigen (also known as KLK3), the pro-urokinase-type plasminogen
225
activator, the fibrinogen and the urokinase-type plasminogen activator receptor. It has also been suggested that KLK4 may initiate intracellular signalling via members of the protease-activated receptor (PAR) family of G protein-coupled receptors. Studies have also associated KLK4 expression with cancer progression suggesting that KLK4’s aggressive proteolytic activity could promote tissue invasion and metastasis. Aim: To evaluate the expression and potential roles of KLK4 in oral squamous cell carcinomas (OSCC). Materials and methods: KLK4 expression was detected by immunohistochemistry, Western blots and zymograms in OSCC cell lines and tumour specimen. Proliferation, invasion, and flow adhesion assays were undertaken using high versus low/undetectable KLK4-expressing OSCC cell lines. Inhibition of KLK4 expression by siRNA was performed to investigate KLK4 roles in OSCC pathogenesis and disease progression. Results: KLK4 expression was differentially expressed in OCSS cell lines and tumour specimen. OSCC cell lines with high invasive and metastatic potential showed the highest levels of KLK4 expression. KLK4 RNA and protein expression was correlated with enzyme activity detected by zymograms. Inhibition of KLK4 expression resulted in diminished invasive and metastatic potential in OSCC cell lines. Consistently, KLK4 expression was stronger in primary OSCC specimens of patients that later developed metastases. Discussion: KLK4 is preferentially expressed in aggressive OSCC cells and might be a novel prognostic tool of OSCC disease outcome and a potential therapeutic target for OSCC treatment. doi:10.1016/j.oos.2009.06.598
P3.73. Evaluation of different oral functions following prosthodontic therapy in cleft patients I. Gitt *, T. Reiber Clinic for Prosthodontics, Dental Materials and Special Care Dentistry, University of Leipzig, Germany Introduction: In Europe clefts belong to the most frequent human malformations with a rate of 1:500 newborns. Beside the primary organic defects appear secondary disorders of speech, chewing and esthetics, which can cause psychosocial disturbances. Prosthodontic treatment is the end of the pre treatment during the first life decades with the aim of restoration the disturbed functions. With this study we examined the importance of different functions in reconstruction of the orofacial system for the patients. Methods: In cooperation with the Univ. Dept of Psychology a questionnaire was elaborated giving us the possibility of anonymity for the 28 patients (22 male, 6 female, mean age 52.1 years).This was followed by a data analysis (biography, patients data, satisfaction with prosthodontic treatment, valuation of importance of the denture for restoration of such functions like speech, chewing, esthetics, satisfaction with the present appearance, present familiar and professional job situation, getting on with the malformation and acceptance by the surrounding. The results were examined statistically. Results: Following treatment the speech function was ‘‘very important” for 68% of the patients, chewing for 57%, esthetical function for 14%. There was a significant correlation between ‘‘age and education” and importance of the esthetic function. Discussion: Resulting from these results we can state, that in this special patientgroup the speech function as mediator for interhuman relations plays the most important role in restoration of the orofacial system by dentures. Only so it is possible to realise a complete social integration for these patients.
Poster Abstracts Oral AbstractsPoster ListOrals ListPan. Disc. & Symp. Abs.Keynote Abs.Keynote Bios.ProgramIAOOWelcomeCommittee Listings
Poster session III / Oral Oncology Supplement 3 (2009) 201–236