Apolipoprotein A1 and Transferrin as Biomarkers in Ovarian Cancer Diagnostics

Macuks, Ronalds; Baidekalna, Ieva; Gritcina, Julia; Avdejeva, Arina; Doniņa, Simona

doi:10.2478/v10163-011-0003-3

Cited by 11 publications

(10 citation statements)

References 23 publications

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“…Zamanian-Daryoush et al, 2013). Apolipoprotein A-1 has been shown to be a biomarker of ovarian cancer and in combination with CA215 increased the sensitivity for ovarian cancer detection (Macuks et al, 2010). In addition, apolipoprotein A-1 has been found to suppress tumor growth and metastasis in multiple animal tumor models, including the B16F10L murine malignant tumor model, in an indirect manner through modulation of the immune system (Zamanian-Daryoush et al, 2013).…”

Section: Anastellinmentioning

confidence: 99%

“…Huang, Wang, Zhang, Li, & Li, 2013) Anastellin 256 (Neskey, Ambesi, Pumiglia, & McKeown-Longo, 2008;Pasqualini, Bourdoulous, Koivunen, Woods, & Ruoslahti, 1996;M. Yi & Ruoslahti, 2001) Apolipoprotein A-1 31 (Macuks et al, 2010;Zamanian-Daryoush et al, 2013) Fibrinogen β chain 56 (Krajewska et al, 2010) Keratin type I cytoskeletal 9 62 (W. Yi et al, 2013) Others: Complement component C4b (Childo blood group) 193 (Markiewski & Lambris, 2009;Rutkowski et al, 2010) …”

Section: Biochemical and Immunological Characterizations Of Ca215-s+ mentioning

confidence: 99%

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Human Serum Proteins Recognized by CA215 and Cancerous Immunoglobulins and Implications in Cancer Immunology

Lee¹,

Liu²,

Huang³

2014

CCO

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In 1987, a monoclonal antibody, RP215, was generated against the OC-3-VGH cancer cell line and shown to react with a carbohydrate-associated epitope located mainly on the heavy chains of immunoglobulins, designated as CA215, which are expressed on the surface of almost all cancer cells and not on normal immune cells. CA215 and cancerous immunoglobulins were affinity-isolated from the shed culture media of the same ovarian cancer cell line by using RP215-linked and anti-human immunoglobulin G-linked affinity chromatography, respectively. They were then immobilized separately as general ligands to isolate any protein components from pooled human sera which demonstrated affinity to CA215 and/or cancerous immunoglobulin G. The affinity-isolated components were then subjected to molecular analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Among the detected protein components, more than 72% were found to be commonly recognized by both CA215 and cancerous immunoglobulins. Some have previously been identified as endogenous proteins or fragments in human serum. They are considered generally, as cancer biomarkers, according to their pro-cancer (e.g. C4b binding protein α chain, complement C3, complement factor H, serotransferrin, and vironectin), anti-cancer (e.g. 35 kDa inter-α-trypsin inhibition heavy chain 4, anastellin, apolipoprotein A-1, fibrinogen β chain, and, keratin type I cytoskeletal 9), or autoimmune (specific immunoglobulin G) properties, respectively. Therefore, besides serving a role for the growth/proliferation of cancer cells, cancerous immunoglobulins can also interact directly or indirectly with many other serum protein components or fragments for unspecified reasons and unknown mechanisms of action.

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Section: Anastellinmentioning

confidence: 99%

Section: Biochemical and Immunological Characterizations Of Ca215-s+ mentioning

confidence: 99%

Human Serum Proteins Recognized by CA215 and Cancerous Immunoglobulins and Implications in Cancer Immunology

Lee¹,

Liu²,

Huang³

2014

CCO

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“…It was also considered as a biomarker of ovarian cancer when combined with CA215 to improve diagnostic sensitivity. Apolipoprotein A-1 was also shown to suppress tumor growth, angiogenesis, metastasis in mouse animal model studies [43,44].…”

Section: Human Serum Proteins Exhibiting Anti-cancer Properties and Imentioning

confidence: 99%

“…Most of these human serum proteins are known to exhibit anti-cancer properties through several previous investigations [39][40][41][42][43][44]. Among these are anastellin, apolipoprotein A1, fibrinogen β-chain and others such as inter-α-trypsin inhibitor and keratin type 1 cytoskeletal 9 [39][40][41][42][43][44][45].…”

Section: Human Serum Proteins Exhibiting Anti-cancer Properties and Imentioning

confidence: 99%

Dual Differential Roles of Cancerous Immunoglobulins as Suggested by Interactions with Human Serum Proteins

Lee¹

2015

J Clin Cell Immunol

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In search of functional roles of immunoglobulins expressed by cancer cells, molecular interactions between cancerous immunoglobulins and human serum proteins or protein fragments were investigated by using RP215 monoclonal antibody as the unique probe. RP215 was initially generated against OC-3-VGH ovarian cancer cell extract and shown to react with carbohydrate-associated epitope located mainly on the variable regions of immunoglobulin heavy chains and others expressed by cancer cells which are designated in general as CA215. CA215 and cancerous immunoglobulins (cIgG) were affinity isolated from the shed medium of cultured cancer cells. Furthermore, by using purified CA215 and cIgG as the respective affinity ligands, the serum proteins or components were affinity isolated and subject to analysis by LCMS/MS methods. The results of such analysis suggest that as many as 80-86% of the isolated human serum proteins were identical in those purified by either affinity column. They are generally classified as pro-cancer and anti-cancer protein components. Among the known pro-cancer protein components recognized by cancerous immunoglobulins are C4 binding proteins α-chain, complement C3, complement factor H, serotransferrin and vitronectin, etc. On the other hand, inter-α-trypsin inhibitor heavy chain 4, anastellin, apolipoprotein A1, fibrinogen β-chain and keratin type 1 cytoskeletal 9 or autoimmune IgG were considered to be anti-cancer proteins from human serum. Based on these observations, dual functional roles of cancerous immunoglobulins are hypothesized. It has been demonstrated in this study that cancerous immunoglobulins are capable of serving as specific binding protein-like immunoglobulins to capture serum proteins to promote growth of cancer cells. At the same time, they can neutralize those with anti-cancer properties in human circulations.

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“…Biomarker of ovarian cancer [89] Net functional effects include a decrease in tumor growth, angiogenesis, metastasis, invasion, & myeloid-derived suppressor cell recruitment, as well as an increase in antitumor macrophages & CD8 + T cells cells [74] Apolipoprotein A-1-deficient mice develop tumors quicker than wild-type mice [74] Fibrinogen β chain First 20 amino acids of the N terminus of the fibrinogen beta chain (β43-63) significantly inhibits VEGF-activated adhesion of epithelial cells to the extracellular matrix [71] In mouse models, inhibits tumor vascularization & increases tumor necrosis [71] Others:…”

Section: Anastellinmentioning

confidence: 99%

Cancerous Immunoglobulins in Cancer Immunology

2014

J Clin Cell Immunol

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The expression of immunoglobulins by cancer cells have been known for two decades. However, the mechanisms of action behind these cancerous immunoglobulins (cIgG) are not well understood and may be different from immunoglobulins secreted by normal B lymphocytes. Therefore, the structural and functional roles of cIgG have been actively investigated to resolve this mystery. A monoclonal antibody, RP215, was generated in 1987 and was shown to react with a carbohydrate-associated epitope localized mainly on the heavy chains of cIgG but not on normal immunoglobulins. The knowledge of cIgG has been greatly advanced by using RP215 as a unique probe. Not only was RP215 shown to act as an anti-cIgG to induce apoptosis of cultured cancer cells in vitro/in vivo, it was also shown to elicit complement-dependent cytotoxicity (CDC) reactions to trigger lysis of cancer cells. It has now been established that besides serving to preserve growth/proliferation of cancer cells by capturing growth factors from the human serum, cIgG may also interact with certain human serum proteins which may be harmful to cancer cells. Thus, the hypothesis of dual functional roles of cIgG can be adequately explained in cancer immunology. Furthermore, RP215 may also be used to target cancer cells with surface bound cIgG for development of antibodybased anti-cancer drugs, provided that bioequivalent humanized RP215 is available for preclinical and clinical studies of immunotherapy.

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Apolipoprotein A1 and Transferrin as Biomarkers in Ovarian Cancer Diagnostics

Cited by 11 publications

References 23 publications

Human Serum Proteins Recognized by CA215 and Cancerous Immunoglobulins and Implications in Cancer Immunology

Human Serum Proteins Recognized by CA215 and Cancerous Immunoglobulins and Implications in Cancer Immunology

Dual Differential Roles of Cancerous Immunoglobulins as Suggested by Interactions with Human Serum Proteins

Cancerous Immunoglobulins in Cancer Immunology

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