Cytogenetic changes during tumor progression towards invasion, metastasis and immune escape in the Eb/ESb model system

1982 ◽  
Vol 30 (5) ◽  
pp. 633-642 ◽  
Author(s):  
R. Dzarlieva ◽  
V. Schirrmacher ◽  
N. F. Fusenig
Keyword(s):  
Tumor Progression ◽  
Immune Escape ◽  
Model System ◽  
Cytogenetic Changes

scholarly journals Nonrandom cytogenetic changes accompany malignant progression in clonal lines abelson virus-infected lymphocytes

Blood ◽  
1994 ◽  
Vol 84 (12) ◽  
pp. 4301-4309 ◽  
Author(s):  
SS Clark ◽  
Y Liang ◽  
CK Reedstrom ◽  
SQ Wu
Keyword(s):  
Tumor Progression ◽  
Murine Leukemia Virus ◽  
Leukemia Virus ◽  
Lymphoid Cells ◽  
Full Transformation ◽  
Cytogenetic Abnormalities ◽  
Cytogenetic Changes ◽  
Abelson Murine Leukemia Virus ◽  
Murine Leukemia ◽  
Over Time

Initially, lymphoid cells transformed by v-abl or BCR/ABL oncogenes are poorly oncogenic but progress to full transformation over time. Although expression of the oncogene is necessary to initiate and maintain transformation, other molecular mechanisms are thought to be required for full transformation. To determine whether tumor progression in ABL oncogene-transformed lymphoid cells has a genetic basis, we examined whether progression of the malignant phenotype of transformed clones correlates with particular cytogenetic abnormalities. A modified in vitro bone marrow transformation model was used to obtain clonal Abelson murine leukemia virus-transformed B lymphoid cells that were poorly oncogenic. Multiple subclones were then derived from each clone and maintained over a marrow-derived stromal cell line for several weeks. Over time, clonally related Abelson murine leukemia virus-transformed subclones progressed asynchronously to full transformation. The data show that tumor progression can occur in the absence of detectable cytogenetic changes but, more importantly, that certain cytogenetic abnormalities appear reproducibly in highly malignant subclones. Therefore, three independent subclones showed deletion in a common region of chromosome 13. Other highly malignant cells carried a common breakpoint in the X chromosome, and, finally, two subclones carried an additional chromosome 5. These results are consistent with the hypothesis that ABL oncogenes are sufficient for the initial transformation of cells but that additional genetic events can drive oncogenic progression. These observations further suggest that diverse genetic mechanisms may be able to drive tumor progression in cells transformed with ABL oncogenes.

scholarly journals The C-X-C Motif Chemokine Ligand 1 Sustains Breast Cancer Stem Cell Self-Renewal and Promotes Tumor Progression and Immune Escape Programs

2021 ◽  
Vol 9 ◽  
Author(s):  
Stefania Livia Ciummo ◽  
Luigi D’Antonio ◽  
Carlo Sorrentino ◽  
Cristiano Fieni ◽  
Paola Lanuti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Cancer Stem Cell ◽  
Tumor Progression ◽  
Immune Escape ◽  
Epithelial Mesenchymal Transition ◽  
Breast Cancer Stem Cell ◽  
Self Renewal ◽  
Mesenchymal Transition ◽  
Mammosphere Formation

Breast cancer (BC) mortality is mainly due to metastatic disease, which is primarily driven by cancer stem cells (CSC). The chemokine C-X-C motif ligand-1 (CXCL1) is involved in BC metastasis, but the question of whether it regulates breast cancer stem cell (BCSC) behavior is yet to be explored. Here, we demonstrate that BCSCs express CXCR2 and produce CXCL1, which stimulates their proliferation and self-renewal, and that CXCL1 blockade inhibits both BCSC proliferation and mammosphere formation efficiency. CXCL1 amplifies its own production and remarkably induces both tumor-promoting and immunosuppressive factors, including SPP1/OPN, ACKR3/CXCR7, TLR4, TNFSF10/TRAIL and CCL18 and, to a lesser extent, immunostimulatory cytokines, including IL15, while it downregulates CCL2, CCL28, and CXCR4. CXCL1 downregulates TWIST2 and SNAI2, while it boosts TWIST1 expression in association with the loss of E-Cadherin, ultimately promoting BCSC epithelial-mesenchymal transition. Bioinformatic analyses of transcriptional data obtained from BC samples of 1,084 patients, reveals that CXCL1 expressing BCs mostly belong to the Triple-Negative (TN) subtype, and that BC expression of CXCL1 strongly correlates with that of pro-angiogenic and cancer promoting genes, such as CXCL2-3-5-6, FGFBP1, BCL11A, PI3, B3GNT5, BBOX1, and PTX3, suggesting that the CXCL1 signaling cascade is part of a broader tumor-promoting signaling network. Our findings reveal that CXCL1 functions as an autocrine growth factor for BCSCs and elicits primarily tumor progression and immune escape programs. Targeting the CXCL1/CXCR2 axis could restrain the BCSC compartment and improve the treatment of aggressive BC.

scholarly journals The Multifaceted Role of Regulatory T Cells in Breast Cancer

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Kevin Kos ◽  
Karin E. de Visser
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Regulatory T Cells ◽  
Tumor Progression ◽  
Immune Cells ◽  
Cancer Biology ◽  
Immune Escape ◽  
Breast Cancer Subtype ◽  
Annual Review ◽  
Publication Date

The microenvironment of breast cancer hosts a dynamic cross talk between diverse players of the immune system. While cytotoxic immune cells are equipped to control tumor growth and metastasis, tumor-corrupted immunosuppressive immune cells strive to impair effective immunity and promote tumor progression. Of these, regulatory T cells (Tregs), the gatekeepers of immune homeostasis, emerge as multifaceted players involved in breast cancer. Intriguingly, clinical observations suggest that blood and intratumoral Tregs can have strong prognostic value, dictated by breast cancer subtype. Accordingly, emerging preclinical evidence shows that Tregs occupy a central role in breast cancer initiation and progression and provide critical support to metastasis formation. Here, Tregs are not only important for immune escape but also promote tumor progression independent of their immune regulatory capacity. Combining insights into Treg biology with advances made across the rapidly growing field of immuno-oncology is expected to set the stage for the design of more effective immunotherapy strategies. Expected final online publication date for the Annual Review of Cancer Biology, Volume 5 is March 4, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

ACQUISITION OF AGONISTIC PROPERTIES OF BICALUTAMIDE IS ASSOCIATED WITH PROSTATE TUMOR PROGRESSION IN A NEW MODEL SYSTEM

1999 ◽  
pp. 59
Author(s):  
Zoran Culig ◽  
Martin Erdel ◽  
Iris E. Eder ◽  
Alfred Hobisch ◽  
Anton Hittmair ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Model System ◽  
Prostate Tumor ◽  
New Model

scholarly journals The role of exosomal PD-L1 in tumor progression and immunotherapy

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Feiting Xie ◽  
Mengxue Xu ◽  
Jian Lu ◽  
Lingxiang Mao ◽  
Shengjun Wang
Keyword(s):  
T Cells ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Immune Checkpoint ◽  
Immune Escape ◽  
Transmembrane Protein ◽  
Biologically Active ◽  
Type I ◽  
Mesenchymal Transition

Abstract Programmed death ligand 1 (PD-L1), a type I transmembrane protein, binds to its receptor PD-1 to suppress the activation of T cells, thereby maintaining immunological homeostasis. In contrast, tumor cells highly express PD-L1, which binds to receptor PD-1 expressed on activated T cells, leading to immune escape. Anti-PD-1/PD-L1 immune checkpoint therapy blocks the binding of PD-1/PD-L1 to reinvigorate the exhausted T cells, thereby inhibiting tumor growth. Exosomes are biologically active lipid-bilayer nanovesicles secreted by various cell types that mediate intercellular signal communication. Numerous studies have shown that tumor cells are able to promote tumor epithelial-mesenchymal transition, angiogenesis, and immune escape by releasing exosomes. Recent studies imply that tumor-derived exosomes could carry PD-L1 in the same membrane topology as the cell surface, thereby resisting immune checkpoint therapy. In this review, we mainly discuss the role of exosomes in the regulation of tumor progression and the potential resistance mechanism to immunotherapy via exosomal PD-L1. In addition, we propose that exosomal PD-L1 may have the potential to be a target to overcome resistance to anti-PD-1/PD-L1 antibody therapy.

scholarly journals Immune Escape during Breast Tumor Progression

2020 ◽  
Vol 8 (4) ◽  
pp. 422-427 ◽  
Author(s):  
Carlos R. Gil Del Alcazar ◽  
Maša Alečković ◽  
Kornelia Polyak
Keyword(s):  
Tumor Progression ◽  
Breast Tumor ◽  
Immune Escape ◽  
Breast Tumor Progression
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