Tumor-specific deposition of immunoglobulin G and complement in papillary thyroid carcinoma

Lucas, Steven; Karlsson‐Parra, Alex; Nilsson, Bo; Grimelius, Lars; Åkerström, Göran; Rastad, Jonas; Juhlin, Claes

doi:10.1016/s0046-8177(96)90346-9

Cited by 82 publications

(71 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Tumor cells may also be a potential target of this system since complement components C4, C3 and C5b-9 are deposited on breast and thyroid carcinoma [2,3]. The complement system has a definite advantage over cytotoxic cells as a defense system because it is made up of soluble molecules that can easily reach the tumor site and diffuse inside the tumor mass.…”

Section: Introductionmentioning

confidence: 99%

Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59

et al. 2005

View full text Add to dashboard Cite

Expression of the complement-regulatory proteins (CRP) CD46, CD55 and CD59 represents a strategy used by tumor cells to evade complement-dependent cell cytoxicity stimulated by monoclonal antibodies. We have isolated two single-chain variable fragments (scFv) to CD55 and CD59 from a human phage-display library and from these scFv we have produced two miniantibodies (MB), MB-55 (against CD55) and MB-59 (against CD59), containing the human hinge-CH2-CH3 domains of IgG1. The specificity of the two MB for the corresponding CRP was assessed by ELISA using purified CD46, CD55 and CD59. MB-55 and MB-59 neutralized the inhibitory activity of CD55 and CD59, respectively, restoring the complement-mediated lysis of sheep and guinea pig erythrocytes that was otherwise inhibited by the two CRP. FACS analysis revealed binding of MB-55 and MB-59 to the lymphoma cell line Karpas 422. The two MB induced a two-fold increase in the complement-dependent killing of these cells stimulated by Rituximab, a chimeric anti-CD20 monoclonal antibody. Transfection of HEK293T cells with vectors encoding MB-55 or MB-59 markedly reduced the expression of CD55 and CD59. We conclude that the human antibodies MB-55 and MB-59 may represent a therapeutic tool to increase the complement-dependent killing activity of Rituximab in the treatment of non-Hodgkin's lymphoma.

show abstract

Section: Introductionmentioning

confidence: 99%

Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59

et al. 2005

View full text Add to dashboard Cite

show abstract

“…9 To date, it is not known whether papillary thyroid cancer cells also produce IgG. Lucas et al, 11 detected cellular deposits of IgG in 80% of 41 papillary thyroid cancer cases studied. They, however, assumed that the presence of IgG was the result of deposition from the serum, and not of local production.…”

mentioning

confidence: 99%

“…They, however, assumed that the presence of IgG was the result of deposition from the serum, and not of local production. 11 Papillary thyroid cancer is the most common endocrine malignancy. 12 It is well differentiated and is one of the most curable cancers.…”

mentioning

confidence: 99%

“…20 In papillary thyroid cancer, C3d, C4d, C5, and C5b-C9 have been detected at the protein level, but it is currently unknown whether complement proteins are also produced by papillary thyroid cancer cells. 11,21 In cancer immunology, complement proteins are thought to contribute to antitumor immune surveillance. 22,23 Mechanisms that might be involved include complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, direct inhibition of tumor growth, and mobilization of hematopoietic progenitor cells.…”

mentioning

confidence: 99%

“…22,23 Mechanisms that might be involved include complement-dependent cytotoxicity, antibody-dependent cell-mediated cytotoxicity, direct inhibition of tumor growth, and mobilization of hematopoietic progenitor cells. 22,23 Lucas et al 11 suggested that the co-expression of IgG and C1q indicated a tumor-specific host immune response with initiation of the classical complement pathway through binding of IgG to tumor antigens. Yamakawa et al 21 demonstrated the expression of membrane complement regulatory proteins (mCRPs), including membrane cofactor protein (CD46), decay-accelerating factor (CD55), and protectin (CD59), and suggested that these factors protect papillary thyroid cancer cells from cell lysis induced by the activation of the complement system.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Immunoglobulin G expression and its colocalization with complement proteins in papillary thyroid cancer

et al. 2012

View full text Add to dashboard Cite

Except for the well-known immunoglobulin G (IgG) producing cell types, ie, mature B lymphocytes and plasma cells, various non-lymphoid cell types, including human cancer cells, neurons, and some specified epithelial cells, have been found to express IgG. In this study, we detected the expression of the heavy chain of IgG (IgGc) and kappa light chain (Igj) in papillary thyroid cancer cells. Using in situ hybridization, we detected the constant region of human IgG1 (IGHG1) in papillary thyroid cancer cells. With laser capture microdissection followed by RT-PCR, mRNA transcripts of IGHG1, Igj, recombination activating gene 1 (RAG1), RAG2, and activation-induced cytidine deaminase genes were successfully amplified from isolated papillary thyroid cancer cells. We further confirmed IgG protein expression with immunohistochemistry and found that none of the IgG receptors was expressed in papillary thyroid cancer. Differences in the level of IgGc expression between tumor size, between papillary thyroid cancer and normal thyroid tissue, as well as between papillary thyroid cancer with and without lymph node metastasis were significant. Taken together, these results indicate that IgG is produced by papillary thyroid cancer cells and that it might be positively related to the growth and metastasis of papillary thyroid cancer cells. Furthermore, it was demonstrated that IgGc colocalized with complement proteins in the same cancer cells, which could indicate that immune complexes were formed. Such immune complexes might consist of IgG synthesized by the host against tumor surface antigens and locally produced anti-idiotypic IgG with specificity for the variable region of these 'primary' antibodies. The cancer cells might thus escape the host tumor-antigen-specific immune responses, hence promoting tumor progression.

show abstract

Aberrantly expressed cytokeratin 1, a tumor-associated autoantigen in papillary thyroid carcinoma

Lucas

Rask

et al. 1997

Int. J. Cancer

Self Cite

View full text Add to dashboard Cite

Tumor-specific deposition of immunoglobulin G and complement in papillary thyroid carcinoma

Cited by 82 publications

References 28 publications

Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59

Controlling complement resistance in cancer by using human monoclonal antibodies that neutralize complement-regulatory proteins CD55 and CD59

Immunoglobulin G expression and its colocalization with complement proteins in papillary thyroid cancer

Aberrantly expressed cytokeratin 1, a tumor-associated autoantigen in papillary thyroid carcinoma

Contact Info

Product

Resources

About