Marie-Paule Van Damme

Monash University (Australia), Melbourne, Victoria, Australia

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Publications (8)27.23 Total impact

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    ABSTRACT: The extracellular glycosaminoglycan hyaluronan (HA) and its degradative enzymes, hyaluronidases (Hyal), play important roles in tumor metastasis and angiogenesis. HA promotes tumor cell adhesion and migration, while its cleaved fragments stimulate angiogenesis. The aims of this study were to assess the levels of HA and how it might be regulated in endometrial cancer. Endometrial carcinomas were grouped according to histologic grade (Grade 1-3). HA histochemistry utilized a biotinylated HA binding peptide (n = 15), while HA synthase (HAS) immunohistochemistry utilized an antibody recognizing HAS1, HAS2 HAS3 (n = 24). Real-time RT-PCR was used to determine the mRNA expression of Hyal 1, Hyal 2 (n = 13) and Hyal 3 (n = 11) in endometrial carcinomas. HA, its synthases and degradative enzymes were identified in endometrial carcinomas of all histologic grades. HA was predominantly localized to tumor-associated stroma. Semiquantitative analysis revealed increased HA levels with tumor grade, however, this increase only attained significance in Grade 2 carcinomas (P < 0.05). HA staining intensity scores were significantly associated with the presence of myometrial invasion (P < 0.05). Alternatively, HAS was predominantly localized in tumor epithelial cells, and its levels did not vary with tumor grade. Expression of Hyal 3 and Hyal 2 mRNA were >1000-fold and >30-fold greater respectively than that of Hyal 1 mRNA, the major Hyal expressed in other cancers. No Hyal type varied with tumor grade. This is the first study to demonstrate the cellular localization of HA and its synthases and that Hyal 3 mRNA is predominant in endometrial cancer. The results suggest a role for elevated HA in endometrial cancer progression.
    Gynecologic Oncology 09/2005; 98(2):193-202. · 3.93 Impact Factor
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    ABSTRACT: Some monoclonal antibodies (mAb) to type II collagen (CII) are arthritogenic upon passive transfer to mice. We undertook this study to investigate whether such mAb are pathogenic in the absence of mediators of inflammation. The arthritogenic mAb CIIC1 and M2139, and the nonarthritogenic mAb CIIF4, each reactive with a distinct and well-defined conformational epitope on CII, were compared with control mAb GAD6. Bovine chondrocytes were cultured with one of the mAb, and on days 3, 6, and 9, antibody binding by chondrocytes and newly synthesized extracellular matrix (ECM) was examined by immunofluorescence, morphologic effects were studied by electron microscopy, and synthesis of matrix components was determined by metabolic labeling with (3)H-proline for collagen and (35)S-sulfate for proteoglycans. All 3 mAb to CII bound to the matrix. CIIC1 and M2139 adversely affected the cultures, whereas CIIF4 did not. CIIC1 caused disorganization of CII fibrils in the ECM without affecting chondrocyte morphology, and increased matrix synthesis. M2139 caused thickening and aggregation of CII fibrils in the ECM and abnormal chondrocyte morphology but matrix synthesis was unaffected. The unique arthritogenic capacity of particular anti-CII mAb upon passive transfer could be explained by their adverse, albeit differing, effects in primary cultures of chondrocytes. Such effects occur independent of inflammation mediators and are related to the epitope specificity of the mAb. Interference with the structural integrity of CII could precede, and even initiate, the inflammatory expression of disease.
    Arthritis & Rheumatology 07/2005; 52(6):1897-906. · 7.48 Impact Factor
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    ABSTRACT: Certain monoclonal antibodies (mAbs) to type II collagen (CII) induce arthritis in vivo after passive transfer and have adverse effects on chondrocyte cultures and inhibit self assembly of collagen fibrils in vitro. We have examined whether such mAbs have detrimental effects on pre-existing cartilage. Bovine cartilage explants were cultured over 21 days in the presence of two arthritogenic mAbs to CII (CIIC1 or M2139), a non-arthritogenic mAb to CII (CIIF4) or a control mAb (GAD6). Penetration of cartilage by mAb was determined by immunofluorescence on frozen sections and correlated with changes to the extracellular matrix and chondrocytes by morphometric analysis of sections stained with toluidine blue. The effects of mAbs on matrix components were examined by Fourier transform infrared microspectroscopy (FTIRM). A possible role of Fc-binding was investigated using F(ab)2 from CIIC1. All three mAbs to CII penetrated the cartilage explants and CIIC1 and M2139, but not CIIF4, had adverse effects that included proteoglycan loss correlating with mAb penetration, the later development in cultures of an abnormal superficial cellular layer, and an increased proportion of empty chondrons. FTIRM showed depletion and denaturation of CII at the explant surface in the presence of CIIC1 or M2139, which paralleled proteoglycan loss. The effects of F(ab)2 were greater than those of intact CIIC1. Our results indicate that mAbs to CII can adversely affect preformed cartilage, and that the specific epitope on CII recognised by the mAb determines both arthritogenicity in vivo and adverse effects in vitro. We conclude that antibodies to CII can have pathogenic effects that are independent of inflammatory mediators or Fc-binding.
    Arthritis research & therapy 02/2005; 7(5):R927-37. · 4.27 Impact Factor
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    ABSTRACT: Antibodies to type II collagen (CII) cause articular damage in collagen-induced arthritis (CIA) in mice as judged by passive transfer to naive animals of mAb to CII. We tested the hypothesis that mAb degrade cartilage structure by reacting with functionally important regions of the collagen molecule by examining the effects of an arthritogenic mAb to CII, CII-C1, on cultured bovine chondrocytes at high density, at days 7 and 14. The effects were compared of CII-C1, an isotype-matched control mAb, or medium alone, on chondrocyte proliferation and viability, cell morphology, matrix structure by light and electron microscopy, and matrix synthesis by metabolic labelling with 3H-proline for collagen or 35SO4 for proteoglycans. Chondrocytes in culture remained viable, proliferated, and produced an extracellular matrix in which CII was the major collagen. The addition of CII-C1, but not a control mAb, increased the synthesis of CII and proteoglycan, and caused disorganization of the extracellular matrix and thin collagen fibrils ultrastructurally. Moreover, using a cell-free assay, CII-C1 inhibited the normal self-assembly of collagen fibrils from CII in solution. The finding that the mAb to CII, CII-C1 has striking degradative effects in vitro on cartilage synthesis suggests that antibodies to collagen perpetuate the chronic phase of CIA and that, in mice at least, such antibodies are an important component of pathogenesis.
    Immunology and Cell Biology 09/2004; 82(4):427-34. · 3.93 Impact Factor
  • Kanda Chaipinyo, Barry W Oakes, Marie-Paule I Van Damme
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    ABSTRACT: Autologous chondrocyte implantation (ACI) is the most promising surgical treatment for large full thickness knee joint articular cartilage (AC) defects where cells from healthy non-weight bearing area AC are multiplied in vitro and implanted into such defects. In the routine surgical procedure for symptomatic knee full thickness AC defects, damaged AC surrounding the edge and the base of such defects is usually debrided and discarded. The purpose of this study was to examine if chondrocytes from this 'debrided' AC can proliferate, synthesize a cartilage specific matrix and thus can be used for ACI. METHODS: Biopsies were retrieved from 12 patients (debrided articular cartilage: DAC, aged 35-61) and from two autopsies (normal articular cartilage: NAC, aged 21 and 25). Chondrocytes were isolated, seeded at low density in type I collagen gels and as monolayer cultures for 4 weeks without passage. RESULTS: After 4 weeks cultures in type I collagen gels, cell proliferation from DAC (18.34 +/- 1.95 fold) was similar to cells from NAC (11.24 +/- 1.02 fold). Syntheses of proteoglycan and collagen in DAC were also similar to NAC. Newly synthesized matrices in gel cultures consisted predominantly of type II collagen as shown by immuno-labelling and SDS-PAGE followed by fluorography. Chondrocytes from 'debrided human AC' cultured at low density in type I collagen gels may be used for the ACI procedure as they provide sufficient viable cell numbers for ACI and maintain their chondrocyte phenotype as they synthesize a cartilage-like matrix.
    Journal of Orthopaedic Research 04/2004; 22(2):446-55. · 2.88 Impact Factor
  • Kanda Chaipinyo, Barry W Oakes, Marie-Paule I van Damme
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    ABSTRACT: Low cell density cell numbers and dedifferentiation are two major problems of human chondrocyte culture associated with articular cartilage repair. Bovine chondrocytes seeded at low density (3.5 x 10(4) cells/ml of gels) in three-dimensional collagen type I gels do proliferate and maintain their phenotype as shown by cell counts, morphology and matrix synthesis. The combination of three growth factors (3GFs; 10 ng/ml TGF-beta1 + 100 ng/ml IGF-I + 10 ng/ml b-FGF) added to serum-free culture medium in this culture system enhances the mitotic activity of bovine chondrocytes similar to 20% foetal calf serum (FCS). At day 21, cells proliferated by 41 fold in gels-FCS and 37 fold in gels-3GFs. Protein synthesis by gels-3GFs cultures was similar to 20% FCS when cultured for 3 weeks but much less proteoglycan was synthesized. The matrix deposition as observed by light and electron microscopy was quite different. More small diameter branching collagen fibrils and a denser matrix were presented in gels-FCS culture whilst loosely arranged larger diameter collagen fibrils were observed in gels-3GFs.
    Journal of Orthopaedic Research 10/2002; 20(5):1070-8. · 2.88 Impact Factor
  • Marianne Tellbach, Lois A Salamonsen, Marie-Paule Van Damme
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    ABSTRACT: The ovine endometrium is subjected to cyclic oscillations of estrogen and progesterone in preparation for implantation. One response to fluctuating hormonal levels is the degree of hydration of the tissue, suggesting cyclical alterations in glycosaminoglycan/proteoglycan content. The aim of the present study was to quantitate and characterize glycosaminoglycans in the ovine endometrium during estrogen and progesterone dominant stages. Endogenous endometrial glycosaminoglycan content was determined by chemical analysis and characterized by enzyme specific or chemical degradation. [(35)S]-sulphate and [(3)H]-glucosamine labeled proteoglycans/glycosaminoglycans were extracted by cell lysis or with 4M guanidine-HCl. Extracts were purified by anion exchange and gel chromatography and characterized as above. Estrogen and progesterone dominant endometrium contained 3.2 +/- 0.1 and 2.1 +/- 0.1 mg endogenous glycosaminoglycan/g dehydrated tissue, respectively. Characterization of endogenous glycosaminoglycan showed chondroitin sulphate and hyaluronan contributing over 80%. The major difference between hormonal dominant tissue was a higher estrogenic hyaluronan percentage and a higher progestational keratan sulphate percentage (p < 0.001). Estrogen dominant tissue incorporated 1.6-1.9 fold more radiolabeled proteoglycans/glycosaminoglycans (p < 0.001). Analysis of newly synthesized proteoglycans/glycosaminoglycans revealed a heparan/chondroitin sulphate ratio of 1:2.2-2.5. Keratan sulphate was not detected. Estrogenic hyaluronan was 1.6 fold greater in [(3)H]-labeled tissue. Analysis of labeled proteoglycans/glycosaminoglycans revealed two size classes with apparent molecular weights >2.0 x 10(6) and 0.8-1.1 x 10(5) and a charge class eluting between 0.1-0.5 M NaCl. The greater glycosaminoglycan content (particularly hyaluronan) and synthesis in estrogen dominant tissue supports a role for steroid hormones in endometrial glycosaminoglycan/proteoglycan regulation and consequent tissue hydration. It also suggests a role for these macromolecules in endometrial function and possibly the implantation process.
    Glycoconjugate Journal 08/2002; 19(6):385-94. · 1.88 Impact Factor
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    Marie-Paule Van Damme, Kaye Trembath
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    ABSTRACT: We have introduced a novel approach to the learning of metabolism by undergraduate students of biochemistry by providing them, on CD-ROM, with an intellectual challenge relating to 'real world' metabolic problems. The CD-ROM Biochemistry -A Metabolic Challenge is an integral component of our course curriculum but has been introduced with different emphasis into the different undergraduate Biochemistry courses. For science students, the programs are an adjunct to formal lectures and part of problem-solving sessions that are a component of the practical classes. For biomedical and medical students, who are high academic achievers, the CD-ROM is also used for self-directed learning and case studies whereby students are expected to take more responsibility for their own learning. The problem-solving exercises, entitled The Great Metabolic Race and The After Race Banquet, explore the metabolic changes that occur to an athlete during a long distance race, and the subsequent recovery phase. The exercises are question/problem based and interactive, requiring students to analyse the questions, think logically and respond by integrating information drawn from a variety of sources. A set of thirteen self-paced, interactive tutorials covering the fundamentals of metabolism are linked to these exercises to act as one resource. While the answers to the questions do not appear in the tutorials, the information required to formulate the answers does. The CD-ROM is used for self-directed learning to help students visualize pathways and the relationship between them, and to integrate the knowledge they have acquired from various sources. It also contains case studies to teach students how these pathways are affected in specific clinical cases. Surveys have shown that students respond particularly well to the participatory nature of this new resource and find the self-paced learning and testing very valuable. We also have preliminary indications that the use of these programs does translate into improved student comprehension as judged by examination performance.