Molecular cloning of Porimin, a novel cell surface receptor mediating oncotic cell death

Ma, Fei; Zhang, Chonghui; Prasad, Kartik; Freeman, Gordon J.; Schlossman, Stuart F.

doi:10.1073/pnas.171322898

Cited by 76 publications

(54 citation statements)

References 27 publications

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“…For example, harakiri (HRK), forkhead box O3 (FOXO3) and leptin (LEP) (24-26) stimulate apoptosis in various cell types, and transmembrane 123 (TMEM123) encodes a mucinlike gene that leads to oncotic cell death upon cross-linking (27).…”

Section: Proliferative and Resting Fractions Exhibit Gene Expression mentioning

confidence: 99%

Intraclonal Complexity in Chronic Lymphocytic Leukemia: Fractions Enriched in Recently Born/Divided and Older/Quiescent Cells

Calissano

Damle

Marsilio

et al. 2011

Mol Med

150

171

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The failure of chemotherapeutic regimens to eradicate cancers often results from the outgrowth of minor subclones with more dangerous genomic abnormalities or with self-renewing capacity. To explore such intratumor complexities in B-cell chronic lymphocytic leukemia (CLL), we measured B-cell kinetics in vivo by quantifying deuterium ( 2 H)-labeled cells as an indicator of a cell that had divided. Separating CLL clones on the basis of reciprocal densities of chemokine (C-X-C motif) receptor 4 (CXCR4) and cluster designation 5 (CD5) revealed that the CXCR4 dim CD5 bright (proliferative) fraction contained more 2 H-labeled DNA and hence divided cells than the CXCR4 bright CD5 dim (resting) fraction. This enrichment was confirmed by the relative expression of two cell cycle-associated molecules in the same fractions, Ki-67 and minichromosome maintenance protein 6 (MCM6). Comparisons of global gene expression between the CXCR4 dim CD5 bright and CXCR4 bright CD5 dim fractions indicated higher levels of pro-proliferation and antiapoptotic genes and genes involved in oxidative injury in the proliferative fraction. An extended immunophenotype was also defined, providing a wider range of surface molecules characteristic of each fraction. These intraclonal analyses suggest a model of CLL cell biology in which the leukemic clone contains a spectrum of cells from the proliferative fraction, enriched in recently divided robust cells that are lymphoid tissue emigrants, to the resting fraction enriched in older, less vital cells that need to immigrate to lymphoid tissue or die. The model also suggests several targets preferentially expressed in the two populations amenable for therapeutic attack. Finally, the study lays the groundwork for future analyses that might provide a more robust understanding of the development and clonal evolution of this currently incurable disease.

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Section: Proliferative and Resting Fractions Exhibit Gene Expression mentioning

confidence: 99%

Intraclonal Complexity in Chronic Lymphocytic Leukemia: Fractions Enriched in Recently Born/Divided and Older/Quiescent Cells

Calissano

Damle

Marsilio

et al. 2011

Mol Med

150

171

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“…A second antibody directed against porimin, a 110-kDa cell surface receptor, induces complement-independent cell death with features of oncosis. Anti-porimin -mediated cell death was preceded by rapid cell aggregation and pore formation on the plasma membrane, cell swelling, and membrane blebbing (14,15). Defining the molecular entities mediating oncosis in these systems may aid in understanding the relationship between these oncotic cell death signals and whether they share common molecular pathways.…”

Section: Discussionmentioning

confidence: 99%

The glycotope-specific RAV12 monoclonal antibody induces oncosis in vitro and has antitumor activity against gastrointestinal adenocarcinoma tumor xenografts in vivo

Loo¹,

Pryer²,

Young³

et al. 2007

Molecular Cancer Therapeutics

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RAV12 is a chimeric antibody that recognizes an N-linked carbohydrate antigen (RAAG12) strongly expressed on multiple solid organ cancers. More than 90% of tumors of colorectal, gastric, and pancreatic origin express RAAG12, and a majority of these tumors exhibit uniform RAAG12 expression. RAV12 exhibits potent cytotoxic activity in vitro against COLO 205 colon tumor cells via an oncotic cell death mechanism. RAV12-treated COLO 205 cells undergo morphologic changes consistent with oncosis, including cytoskeletal rearrangement, rapid plasma membrane swelling, and cell lysis. RAV12 inhibited the growth of RAAG12-expressing gastrointestinal tumor xenografts in athymic mice. In the case of SNU-16 tumor cells, twice weekly treatment of established s.c. tumors with 10 mg/kg RAV12 caused a f70% suppression of tumor growth at the end of the study. This preclinical data has led to the initiation of a phase I/IIA clinical study of RAV12 in patients with metastatic or recurrent adenocarcinoma. [Mol Cancer Ther 2007;6(3):856 -65]

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“…46 Cells transfected with this receptor were also killed by this antibody with cell membrane injury. 47 RAV12 is a chimeric antibody that recognizes the N-linked carbohydrate antigen RAAG12. 48,49 It was constructed from the mouse mAb KID3.…”

confidence: 99%

“…48 No data are available for the anti-Porimin mAb. 46,47 In summary, there are similarities in the killing mechanism exerted by the above described mAbs (Table 1); nevertheless, the relative contribution for this activity of both the antibody isotype and the nature of the antigen recognized on the target cells is not fully elucidated.…”

confidence: 99%

Lonely killers

Fernández-Marrero

López‐Requena²

2011

mAbs

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Molecular cloning of Porimin, a novel cell surface receptor mediating oncotic cell death

Cited by 76 publications

References 27 publications

Intraclonal Complexity in Chronic Lymphocytic Leukemia: Fractions Enriched in Recently Born/Divided and Older/Quiescent Cells

Intraclonal Complexity in Chronic Lymphocytic Leukemia: Fractions Enriched in Recently Born/Divided and Older/Quiescent Cells

The glycotope-specific RAV12 monoclonal antibody induces oncosis in vitro and has antitumor activity against gastrointestinal adenocarcinoma tumor xenografts in vivo

Lonely killers

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