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The 37kDa/67kDa laminin receptor (LRP/LR) is thought to play a major role in the adhesion to laminin and consequently invasion resulting in the metastasis of tumor cells. This receptor is reported to be over-expressed in several neoplastic cell lines and is believed to increase tumor aggressiveness. This research aims at determining whether the application of anti-LRP/LR specific antibody (IgG1-iS18) on neoplastic cell lines would result in a decrease in invasion and adhesion. All neoplastic cell lines had significantly increased cell surface LRP/LR levels compared to NIH/3T3 cells, with the most notable increase seen in SW480 cells (10.98%). Due to a positive correlation between the cell surface LRP/LR levels and invasion potential we propose that an increased LRP/LR level correlates to an increased ability to invade. A significantly decreased adhesion potential was noted in all neoplastic cell lines except the non-invasive MCF-7 cell line, upon application of IgG1-iS18, 21% decrease in HT-1080 cells, 14% in HeLa, 20% in LNCaP, 48% and 74% in A549 and SW480 cells, respectively. Incubation with the anti-LRP/LR antibody IgG1-iS18 resulted in a significant reduction of the invasive potential of HT-1080 (44%), A549 (33%), HeLa (69%), SW480 (91%) and LNCaP cells (38%). Furthermore, a high Pearson’s correlation coefficient between adhesion potential and invasive potential was seen, confirming that adhesion is indeed a pre-requisite for invasion. The significant reduction in invasion and adhesion of HT-1080, A549, HeLa, SW480 and LNCaP cells upon application of the IgG1-iS18 antibody suggests that this macromolecule might act as a promising therapeutic tool for the treatment of various metastatic cancer types.

Chui Shiu Hon. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 144-183. / ACKNOWLEDGEMENTS / SUMMARY / LIST OF ABBREVIATIONS / Chapter CHAPTER 1. --- INTRODUCTION --- p.1 / Chapter 1.1 --- IgA Nephropathy --- p.1 / Chapter 1.1.1 --- History & Epidemiology --- p.1 / Chapter 1.1.2 --- Clinical Pathological Features --- p.2 / Chapter 1.1.3 --- Laboratory Findings --- p.3 / Chapter 1.1.4 --- Immunopathogenesis --- p.5 / Chapter 1.2 --- The Role of IgA in the Pathogenesis of IgA Nephropathy --- p.10 / Chapter 1.2.1 --- Structure of IgA Molecule --- p.10 / Chapter 1.2.2 --- IgA Biosynthesis and Immune Regulation --- p.23 / Chapter 1.2.3 --- Biological Role of IgA --- p.26 / Chapter 1.2.4 --- Circulating Immune Complexes in IgA Nephropathy --- p.27 / Chapter 1.2.5 --- IgA Subclasses in IgA Nephropathy --- p.32 / Chapter 1.2.6 --- Light Chain Composition of IgA in IgA Nephropathy --- p.33 / Chapter 1.3 --- Aim of the Present Study --- p.36 / Chapter 1.4 --- Design of Experiments --- p.37 / Chapter CHAPTER 2. --- MATERIALS & METHODS --- p.42 / Chapter 2.1 --- Materials --- p.42 / Chapter 2.1.1 --- Patients --- p.42 / Chapter 2.1.2 --- Controls --- p.43 / Chapter 2.1.3 --- Additional Specimens --- p.43 / Chapter 2.1.4 --- Serum Samples --- p.44 / Chapter 2.1.5 --- Chemicals --- p.44 / Chapter 2.1.6 --- Immunoglobulins --- p.46 / Chapter 2.1.7 --- Antisera --- p.47 / Chapter 2.1.8 --- Solutions and Buffers --- p.48 / Chapter 2.1.9 --- Apparatus and Equipment --- p.51 / Chapter 2.2 --- Methods --- p.53 / Chapter 2.2.1 --- Serum Protein Electrophoresis --- p.53 / Chapter 2.2.2 --- Immunochemical Techniques --- p.54 / Chapter 2.2.3 --- Fast Protein Liquid Chromatography (FPLC) for Isolation of Serum IgA --- p.64 / Chapter CHAPTER 3. --- SERUM PROTEIN ELECTROPHORESIS AND IMMUNOGLOBULIN CONCENTRATIONS --- p.67 / Chapter 3.1 --- Serum Protein Electrophoresis --- p.67 / Chapter 3.2 --- Serum Immunoglobulin Concentration --- p.67 / Chapter 3.3 --- Discussion --- p.70 / Chapter CHAPTER 4. --- LIGHT CHAIN RATIOS OF INDIVIDUAL IMMUNOGLOBULINS --- p.72 / Chapter 4.1 --- Enzyme-Linked Immunosorbent Assay for Light Chain Concentrations --- p.72 / Chapter 4.2 --- Light Chain Ratios of Individual Serum Immunoglobulins in Normal Subjects and in Disease --- p.75 / Chapter 4.3 --- Discussion --- p.77 / Chapter CHAPTER 5. --- IN VITRO SYNTHESIS OF IgA WITH LAMBDA LIGHT CHAIN IN IgA NEPHROPATHY --- p.83 / Chapter 5.1 --- Lymphocyte Culture and In Vitro Immunoglobulin Production --- p.83 / Chapter 5.2 --- In Vitro Immunoglobulin Production and Predominant Synthesis of IgA with λ Light Chain in IgA Nephropathy --- p.83 / Chapter 5.3 --- Dicussion --- p.87 / Chapter CHAPTER 6. --- PURIFICATION OF SERUM IgA BY AFFINITY CHROMATOGRAPHY --- p.90 / Chapter 6.1 --- Fast Protein Liquid Chromatography --- p.90 / Chapter 6.2 --- Recovery of Isolated IgA --- p.92 / Chapter 6.3 --- Purity of Isolated IgA --- p.92 / Chapter 6.4 --- κ/λ Ratio of IgA Before and After FPLC --- p.96 / Chapter 6.5 --- Subclass of IgA Before and After FPLC --- p.97 / Chapter 6.6 --- Discussion --- p.100 / Chapter CHAPTER 7. --- "ANALYSIS OF CHARGE DISTRIBUTION OF IgA, IgA(κ) AND IgA(λ)" --- p.102 / Chapter 7.1 --- "Iso-Electric Focusing, Immunoblotting, and Densitometry of Purified IgA for Total IgA, IgA(κ) and IgA (λ)" --- p.102 / Chapter 7.2 --- "Charge Distribution of Plasma Total IgA, IgA(κ) and IgA(λ)" --- p.103 / Chapter 7.2.1 --- A/C Ratio of Total IgA --- p.103 / Chapter 7.2.2 --- A/C Ratio of IgA(κ) --- p.113 / Chapter 7.2.3 --- A/C Ratio of IgA(λ) --- p.113 / Chapter 7.3 --- Discussion --- p.129 / Chapter CHAPTER 8. --- GENERAL DISCUSSION --- p.134 / REFERENCES --- p.140 / APPENDICES

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