A novel anti-Thy-1 (CD90) monoclonal antibody induces apoptosis in mouse malignant T-lymphoma cells in spite of inducing bcl-2 expression

Fujita, Naoya; Kato, Yoshinori; Naito, Mikihiko; Tsuruo, Takashi

doi:10.1002/(sici)1097-0215(19960516)66:4<544::aid-ijc20>3.0.co;2-6

Cited by 22 publications

(9 citation statements)

References 14 publications

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“…Although the exact mechanism through which anti-CD90 mAb exerts its effect is unknown, it was demonstrated that anti-CD90 mAb induced apoptosis in murine T-lymphoma cells through caspase activation and downregulation of antiapoptotic bcl-2 family members [42]. Furthermore, anti-CD90 mAb induced both apoptosis and necrosis in B-cell lymphoma cells, and it has been suggested that anti-CD90 mAb also leads to arrest of the cell cycle, because a discrepancy was observed between the percentage of proliferation inhibition and the number of apoptotic or necrotic B-cell lymphoma cells [41].…”

Section: Discussionmentioning

confidence: 99%

Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas

Buishand

Arkesteijn

Feenstra

et al. 2016

Stem Cells and Development

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The long-term prognosis after surgical resection of malignant insulinoma (INS) is poor. Novel adjuvant therapies, specifically targeting cancer stem cells (CSCs), are warranted. Therefore, the goal of this study was to characterize and target putative INS CSCs. Using fluorescence-activated cell sorting, human INS cell line CM and pancreatic carcinoid cell line BON1 were screened for the presence of stem cell-associated markers. CD90, CD166, and GD2 were identified as potential CSC markers. Only CD90 + INS cells had an increased tumor-initiating potential in athymic nude mice. Anti-CD90 monoclonal antibodies decreased the viability and metastatic potential of injected cells in a zebrafish embryo INS xenograft model. Primary INS stained positive for CD90 by immunohistochemistry, however also intratumoral fibroblasts and vascular endothelium showed positive staining. The results of this study suggest that anti-CD90 monoclonals form a potential novel adjuvant therapeutic modality by targeting either INS cells directly, or by targeting the INS microenvironment.

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Section: Discussionmentioning

confidence: 99%

Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas

Buishand

Arkesteijn

Feenstra

et al. 2016

Stem Cells and Development

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“…This protein is involved in T-cell activation (23) and has widespread nonimmunologic functions, including inhibition of neurite outgrowth (24), apoptotic signaling (25), leukocyte and melanoma cell adhesion and migration (26,27), tumor suppression (28,29), and fibroblast proliferation and migration (30)(31)(32). It is an important marker of mesenchymal stem cells being associated with development, cancer, and CSC.…”

Section: Discussionmentioning

confidence: 99%

“…CD90 or THY-1 was originally discovered as a thymocyte antigen (19,20) but further reports have shown expression of this protein in human fibroblasts, neurons, endothelial cells, as well as in murine T-cells (21,22). This protein is involved in T-cell activation (23) and has widespread nonimmunologic functions, including inhibition of neurite outgrowth (24), apoptotic signaling (25), leukocyte and melanoma cell adhesion and migration (26,27), tumor suppression (28,29), and fibroblast proliferation and migration (30)(31)(32). It is an important marker of mesenchymal stem cells being associated with development, cancer, and CSC.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

et al. 2012

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The recently emerged concept of cancer stem cell (CSC) has led to a new hypothesis on the basis for tumor progression. Basically, the CSC theory hypothesizes the presence of a hierarchically organized and relatively rare cell population, which is responsible for tumor initiation, self-renewal, and maintenance, in addition to accumulation of mutation and resistance to chemotherapy. CSCs have recently been described in breast cancer. Different genetic markers have been used to isolate breast CSCs, none of which have been correlated with the tumorigenicity or metastatic potential of the cells, limiting their precise characterization and clinical application in the development of therapeutic protocols. Here, we sought for subpopulations of CSCs by analyzing 10 judiciously chosen stem cell markers in a normal breast cell line (MCF10-A) and in four human breast cancer cell lines (MCF-7, MDA-MB-231, MDA-MB-435, and Hs578-T) displaying different degrees of metastatic and invasiveness potential. We were able to identify two markers, which are differentially expressed in nontumorigenic versus tumor cells. The CD90 marker was highly expressed in the malignant cell lines. Interestingly, the CD14 molecule displayed higher expression levels in the nontumorigenic cell line. Therefore, we demonstrated that these two markers, which are more commonly used to isolate and characterize stem cells, are differentially expressed in breast tumor cells, when compared with nontumorigenic breast cells. ' 2012 International Society for Advancement of Cytometry Key terms CD90; Thy-1; breast cancer; cancer stem cell; CD14; breast cancer stem cell

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“…In CS-21, a malignant lymphoma cell line, cross-linking of Thy-1 is reported to increase apoptosis [46]. Further cross-linking of other cell death molecules such as in the Fas-Fas ligand system [47] or TNF-mediated cell death [48] also results in enhancement of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

C1q, a subunit of the first component of complement, enhances antibody-mediated apoptosis of cultured rat glomerular mesangial cells

Sato

Dixhoorn

Heemskerk

et al. 1997

Clinical and Experimental Immunology

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SUMMARYWe have shown previously that IgG2a anti-Thy-1 MoAb (ER4G) induces apoptosis of rat mesangial cells (GMC) in vitro. Since the classical complement pathway plays an essential role in Thy-1 nephritis, we analysed whether C1q, a subunit of the first component of complement, enhances the ER4G-mediated apoptosis of rat GMC. Two different subclasses of anti-Thy-1 MoAb, ER4G (IgG2a) and ER14 (IgG1), were used. It was established that ER4G binds C1q efficiently, while ER14 reacts poorly with C1q. For the experiments of apoptosis, quiescent rat GMC were exposed for 1 h at 37ЊC to a fixed concentration of anti-Thy-1 MoAb and incubated further for 16 h at 37ЊC in the presence or absence of C1q. GMC exposed to medium (M-GMC) followed by incubation of the cells with medium alone was used as controls. Apoptosis was assessed by morphological studies and quantitative analysis on FACS using FITC-annexin V (the annexin V methods) or bicolour FACS analysis using FITC-annexin V and propidium iodide (the annexin V/PI method). With the annexin V method, M-GMC revealed 9 . 4 Ϯ 1 . 4% apoptosis. C1q had only marginal effects on apoptosis of M-GMC. GMC exposed to ER4G (ER4G-GMC) and further incubated with medium in the absence of C1q resulted in 25 . 7 Ϯ 5 . 7% apoptosis (P < 0.01 relative to control). Incubation of ER4G-GMC together with 100 mg/ml of C1q significantly increased GMC-apoptosis up to 39 . 4 Ϯ 4 . 9% (P < 0 . 01 relative to ER4G-GMC incubated in the absence of C1q). This enhancing effect of C1q on apoptosis of ER4G-GMC was time-and dose-dependent. In contrast, C1q did not significantly alter the apoptosis of either GMC exposed to ER14 (ER14-GMC) or to F(ab 0 ) 2 -ER4G (F(ab 0 ) 2 -ER4G-GMC), while ER14-GMC or F(ab 0 ) 2 -ER4G-GMC incubated with medium resulted in significant apoptosis compared with control. These results were supported by morphological studies and bicolour FACS analyses in time course experiments using the annexin V/PI method. The effect of C1q is dependent on the presence of intact C1q-containing globular heads and does not occur with collagen-like fragments of C1q. Furthermore, incubation of ER4G-GMC with antimouse k-chain antibodies also increased ER4G-mediated GMC-apoptosis. These results indicate for the first time that C1q enhances antibody-mediated apoptosis of rat GMC in vitro, presumably by its binding to ER4G and probably by additional cross-linking of Thy-1 on the surface of GMC.

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A novel anti-Thy-1 (CD90) monoclonal antibody induces apoptosis in mouse malignant T-lymphoma cells in spite of inducing bcl-2 expression

Cited by 22 publications

References 14 publications

Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas

Identification of CD90 as Putative Cancer Stem Cell Marker and Therapeutic Target in Insulinomas

Differential expression of CD90 and CD14 stem cell markers in malignant breast cancer cell lines

C1q, a subunit of the first component of complement, enhances antibody-mediated apoptosis of cultured rat glomerular mesangial cells

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