Proliferative processes and features of tumor cell receptor apparatus of the breast carcinoma

AbstractTransfer of tumor-specific T-cell receptor (TCR) genes into patient T cells is a promising strategy in cancer immunotherapy. We describe here a novel vector (CD8-LV) derived from lentivirus, which delivers genes exclusively and specifically to CD8+ cells. CD8-LV mediated stable in vitro and in vivo reporter gene transfer as well as efficient transfer of genes encoding TCRs recognizing the melanoma antigen tyrosinase. Strikingly, T cells genetically modified with CD8-LV killed melanoma cells reproducibly more efficiently than CD8+ cells transduced with a conventional lentiviral vector. Neither TCR expression levels, nor the rate of activation-induced death of transduced cells differed between both vector types. Instead, CD8-LV transduced cells showed increased granzyme B and perforin levels as well as an up-regulation of CD8 surface expression in a small subpopulation of cells. Thus, a possible mechanism for CD8-LV enhanced tumor cell killing may be based on activation of the effector functions of CD8+ T cells by the vector particle displaying OKT8-derived CD8-scFv and an increase of the surface density of CD8, which functions as coreceptor for tumor-cell recognition. CD8-LV represents a powerful novel vector for TCR gene therapy and other applications in immunotherapy and basic research requiring CD8+ cell-specific gene delivery.

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A new CD44v3-containing isoform is involved in tumor cell growth and migration during human breast carcinoma progression

Frontiers in Bioscience ◽

10.2741/kalish ◽

1999 ◽

Vol 4 (1-3) ◽

pp. a1 ◽

Cited By ~ 27

Author(s):

Eric, D. Kalish

Keyword(s):

Cell Growth ◽

Breast Carcinoma ◽

Tumor Cell ◽

Human Breast Carcinoma ◽

Tumor Cell Growth ◽

Human Breast ◽

Cell Growth And Migration ◽

And Migration

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Site-Directed Perturbation of Protein Kinase C- Integrin Interaction Blocks Carcinoma Cell Chemotaxis

Molecular and Cellular Biology ◽

10.1128/mcb.22.16.5897-5911.2002 ◽

2002 ◽

Vol 22 (16) ◽

pp. 5897-5911 ◽

Cited By ~ 74

Author(s):

Maddy Parsons ◽

Melanie D. Keppler ◽

Adam Kline ◽

Anthea Messent ◽

Martin J. Humphries ◽

...

Keyword(s):

Protein Kinase ◽

Breast Carcinoma ◽

Tumor Cell ◽

Carcinoma Cell ◽

Carcinoma Cells ◽

Cell Phenotype ◽

Β1 Integrin ◽

Breast Carcinoma Cells ◽

Tumor Cell Motility ◽

Cell Chemotaxis

ABSTRACT Polarized cell movement is an essential requisite for cancer metastasis; thus, interference with the tumor cell motility machinery would significantly modify its metastatic behavior. Protein kinase Cα (PKCα) has been implicated in the promotion of a migratory cell phenotype. We report that the phorbol ester-induced cell polarization and directional motility in breast carcinoma cells is determined by a 12-amino-acid motif (amino acids 313 to 325) within the PKCα V3 hinge domain. This motif is also required for a direct association between PKCα and β1 integrin. Efficient binding of β1 integrin to PKCα requires the presence of both NPXY motifs (Cyto-2 and Cyto-3) in the integrin distal cytoplasmic domains. A cell-permeant inhibitor based on the PKC-binding sequence of β1 integrin was shown to block both PKCα-driven and epidermal growth factor (EGF)-induced chemotaxis. When introduced as a minigene by retroviral transduction into human breast carcinoma cells, this inhibitor caused a striking reduction in chemotaxis towards an EGF gradient. Taken together, these findings identify a direct link between PKCα and β1 integrin that is critical for directed tumor cell migration. Importantly, our findings outline a new concept as to how carcinoma cell chemotaxis is enhanced and provide a conceptual basis for interfering with tumor cell dissemination.

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Expression and prognostic role of SGTA in human breast carcinoma correlates with tumor cell proliferation

Journal of Molecular Histology ◽

10.1007/s10735-014-9586-z ◽

2014 ◽

Vol 45 (6) ◽

pp. 665-677 ◽

Cited By ~ 11

Author(s):

Ting Zhu ◽

Zhengxiang Ji ◽

Caixia Xu ◽

Zhiyang Peng ◽

Liang Gu ◽

...

Keyword(s):

Cell Proliferation ◽

Breast Carcinoma ◽

Tumor Cell ◽

Human Breast Carcinoma ◽

Tumor Cell Proliferation ◽

Human Breast ◽

Prognostic Role

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Flow cytometry of breast carcinoma: II. Relation of tumor cell cycle distribution to histology and estrogen receptor

Cancer ◽

10.1002/1097-0142(19810815)48:4<985::aid-cncr2820480422>3.0.co;2-q ◽

1981 ◽

Vol 48 (4) ◽

pp. 985-988 ◽

Cited By ~ 68

Author(s):

Wlodzimierz Olszewski ◽

Zbigniew Darzynkiewicz ◽

Paul Peter Rosen ◽

Morton K. Schwartz ◽

M. R. Melamed

Keyword(s):

Cell Cycle ◽

Flow Cytometry ◽

Estrogen Receptor ◽

Breast Carcinoma ◽

Tumor Cell ◽

Cell Cycle Distribution

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Chemoimmunotherapy of stage III breast carcinoma with BCG and a live allogeneic tumor cell vaccine

Cancer Immunology Immunotherapy ◽

10.1007/bf00200143 ◽

1979 ◽

Vol 5 (4) ◽

Author(s):

DariaH. Pardridge ◽

F.C. Sparks ◽

J.E. Goodnight ◽

IreneK. Spears ◽

D.L. Morton

Keyword(s):

Breast Carcinoma ◽

Tumor Cell ◽

Stage Iii ◽

Cell Vaccine ◽

Tumor Cell Vaccine ◽

Allogeneic Tumor ◽

Allogeneic Tumor Cell

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Tumor cell expression of HLA-DM associates with a Th1 profile and predicts improved survival in breast carcinoma patients

International Immunology ◽

10.1093/intimm/dxl092 ◽

2006 ◽

Vol 18 (11) ◽

pp. 1591-1602 ◽

Cited By ~ 37

Author(s):

S. A. Oldford ◽

J. D. Robb ◽

D. Codner ◽

V. Gadag ◽

P. H. Watson ◽

...

Keyword(s):

Breast Carcinoma ◽

Tumor Cell ◽

Cell Expression

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Molecular profiling of circulating tumor cells in the peripheral blood of patients with primary and metastatic breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.20033 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 20033-20033

Author(s):

N. Fersis ◽

V. Deckwart ◽

A. Leitz ◽

M. Weber ◽

J. Rom ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Breast Carcinoma ◽

Tumor Cell ◽

Cancer Patients ◽

Tumor Cells ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Rt Pcr ◽

Her 2

20033 Background: The purpose of this study was detection and expression profiling of circulating tumor cells (CTC) in breast cancer patients. Methods: Two separate probes of 5 mL peripheral EDTA-blood from patients with primary breast cancer (n=167) and metastatic disease (n=111) were used for immunomagnetic tumor cell selection. Targets for preanalytical enrichment were the antigens EpCAM and MUC-1. Separated cells were lysed and used for mRNA isolation and c-DNA synthesis. The breast carcinoma-associated transcripts EpCAM, MUC-1, HER-2, claudin7, cytokeratin 19, mammaglobin 1, prostate-specific ets factor (PSE) and survivin were amplified by three separate multiplex RT-PCR reactions. Amplicons were analysed by capillary electrophoresis with the Agilent Bioanalyzer 2100. Specificity of the RT-PCR was confirmed by examination of blood of healthy donors. Results: Sensitivity for every single transcript was adjusted to 2 tumor cells per 5 ml blood. Tumor-associated transcripts were detected in 31 of of 167 (18.5%) patients with primary breast cancer and in 46 of 111 (41%) patients with metastatic disease. The marker with the highest incidence in both groups was MUC-1, with a positivity rate of 81%. Tumor-associated transcripts were heterogenouosly expressed, however multiple markers were identified in more than 50% of the positive samples. Conclusion: Using a combination of preanalytical immunomagnetic tumor cell enrichment followed by a multigen RT-PCR approach we describe a sensitive detection system for breast carcinoma cells. In this study a panel of 8 genes overexpressed at high levels in metastatic breast cancer was selected for the identification of disseminated tumor cells in the peripheral blood of breast cancer patients. HER-2, survivin as a unique member of the inhibitor of apotosis protein family, as well as PSE identified in circulating breast cancer cells may serve as prognostic indicators of tumor progression and could represent valid targets for new individualized therapeutic interventions. No significant financial relationships to disclose.

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