Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines

Cavazzoni, Andrea; Alfieri, Roberta; Cretella, Daniele; Saccani, Francesca; Ampollini, Luca; Galetti, Mauro; Quaini, Federico; Graiani, Gallia; Madeddu, Denise; Mozzoni, Paola; Galvani, Elena; Monica, Silvia La; Bonelli, Mara; Fumarola, Claudia; Mutti, Antonio; Carbognani, Paolo; Tiseo, Marcello; Barocelli, Elisabetta; Petronini, Pier Giorgio; Ardizzoni, Andrea

doi:10.1186/1476-4598-11-91

Cited by 37 publications

(35 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…EGFR is a transmembrane protein that its overexpression and overactivity in cancer cells leads to changes in biological, chemical, and physical activities of cells. 23,24 Live/dead assay Live/dead assay was performed to determine the cell viability among study groups. 21,23 In this study, EGFR was targeted by Cetuximab which bound to the extracellular domain of EGFR and prevented the receptor dimerization.…”

Section: Methodsmentioning

confidence: 99%

“…21,22 EGFR and its various downstream signaling pathways have been considered as a therapeutic strategy in the cancer treatment. 21,23 In this study, EGFR was targeted by Cetuximab which bound to the extracellular domain of EGFR and prevented the receptor dimerization. To treat the cancer cells by Cetuximab, cells were exposed to a culture medium supplemented with 10 μg/mL Cetuximab (Merck) for 24 h. The chosen concentration was below the reported peak plasma concentration of this drug.…”

Section: Methodsmentioning

confidence: 99%

“…To treat the cancer cells by Cetuximab, cells were exposed to a culture medium supplemented with 10 μg/mL Cetuximab (Merck) for 24 h. The chosen concentration was below the reported peak plasma concentration of this drug. 23,24 Live/dead assay Live/dead assay was performed to determine the cell viability among study groups. A cellstain double staining kit (Sigma Aldrich) was used according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations

Azadi

Tafazzoli-Shadpour

Soleimani

et al. 2019

J Biomedical Materials Res

View full text Add to dashboard Cite

To date, a myriad of strategies has been suggested for targeting the chemical signaling of cancer cells. Also, biomechanical features are gaining much more attention. These features can be used as biomarkers which influence cancer progression. Current approaches on cancer treatment are mainly focused on changing the biochemical signaling of cancer cells, whereas less attention was devoted to their biomechanical properties. Herein, we propose targeting of cancer cell mechanics through the microenvironmental mechanical and chemical cues. As such, we examined the role of substrate stiffness as well as the effect of epidermal growth factor receptor (EGFR) blockade in the cell mechanics. As a mechanical stimulus, stiff and soft polydimethylsiloxane substrates were utilized, while as a chemical stimulus, EGFR blockade was considered. Thus, breast cancer cell lines, MCF7 and MDA‐MB‐231, were cultured among chemical and mechanical groups. The local elasticity of cancer cells was assessed by atomic force microscopy nanoindentation method. Furthermore, we evaluated the effect of mentioned mechanical and chemical treatments on the morphology, actin cytoskeleton structures, and cancer cell migration abilities. The stiffness and migration ability of cancer cells increased by substrate stiffening while Cetuximab treatment demonstrated an elevation in the elastic modulus of cells followed by a reduction in the migration ability. These findings indicate that cancer cell mechanics is modulated not only by the mechanical cues but also by the chemical ones through EGFR signaling pathway. Overall, our results illustrate that manipulation of cell mechanics allows for the possible modulation of tumor cell migration. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1569–1581, 2019.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations

Azadi

Tafazzoli-Shadpour

Soleimani

et al. 2019

J Biomedical Materials Res

View full text Add to dashboard Cite

show abstract

“…mTORC1 inhibition leads to the activation of the ERK/MAPK cascade. However, PI3K inhibition using LY294002 reduced rapamycin-induced ERK activation [13]. Furthermore, NVP-BKM120 inhibited mTOR downstream activation, but induced the phosphorylation of AKT and ERK in KRAS mutant gastric cancer cells [14].…”

Section: Discussionmentioning

confidence: 96%

Targeting the PI3K signaling pathway in KRAS mutant colon cancer

Kim

Kang

et al. 2015

Cancer Medicine

View full text Add to dashboard Cite

Metastatic colorectal cancer (CRC) patients with v‐Ki‐ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are resistant to monoclonal antibody that targets the epidermal growth factor receptor such as cetuximab. BKM120 targets phosphatidylinositide‐3‐kinase (PIK3CA), but it is unknown whether BKM120 can reverse cetuximab resistance in KRAS mutant CRC. Human CRC cell lines with KRAS mutations (DLD‐1, HCT116, and LoVo) were used to test the effect of cetuximab, BKM120, and cetuximab plus BKM120 on cell proliferation in vitro and in vivo. BKM120 reduced cell proliferation in a concentration‐dependent manner in the LoVo (PI3KCA wild type) as well as the HCT116 and DLD1 cells (that carry a PI3KCA mutation). BKM120 only inhibited ERK phosphorylation in LoVo cells (PIK3CA wild type), but not in DLD1 or HCT116 cells at a concentration of 1 μmol/L. Treatment with cetuximab and BKM120 significantly reduced the growth of xenograft tumors originating from KRAS mutant cells compared with cetuximab alone (P = 0.034). BKM120 may overcome cetuximab resistance in colon cancer cells with KRAS mutation.

show abstract

“…For the determination of membrane levels of PD-L1, cells were treated for 3 days with chemotherapeutic drugs, collected, and incubated with phycoerythrin (PE) isotype control mouse IgG1 κ or PE anti-human PD-L1 (BD Biosciences, San Jose, CA, USA). After incubation, quantification was performed with a Beckman FC500 flow cytometer as previously described [34] and analyzed with FCS express software (De Novo software, Pasadena, CA, USA). The values of mean fluorescence intensity (MFI) were converted into units of equivalent fluorochrome (MEF) using the FluoroSpheres 6-Peak kit (Dako, Santa Clara, CA, USA).…”

Section: Flow Cytometrymentioning

confidence: 99%

Pemetrexed Enhances Membrane PD-L1 Expression and Potentiates T Cell-Mediated Cytotoxicity by Anti-PD-L1 Antibody Therapy in Non-Small-Cell Lung Cancer

Cavazzoni

Digiacomo

Alfieri

et al. 2020

Cancers

Self Cite

View full text Add to dashboard Cite

Immunotherapy has significantly changed the treatment landscape for advanced non-small-cell lung cancer (NSCLC) with the introduction of drugs targeting programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1). In particular, the addition of the anti-PD-1 antibody pembrolizumab to platinum-pemetrexed chemotherapy resulted in a significantly improved overall survival in patients with non-squamous NSCLC, regardless of PD-L1 expression. In this preclinical study, we investigated whether chemotherapy can modulate PD-L1 expression in non-squamous NSCLC cell lines, thus potentially affecting immunotherapy efficacy. Among different chemotherapeutic agents tested, only pemetrexed increased PD-L1 levels by activating both mTOR/P70S6K and STAT3 pathways. Moreover, it also induced the secretion of cytokines, such as IFN-γ and IL-2, by activated peripheral blood mononuclear cells PBMCs that further stimulated the expression of PD-L1 on tumor cells, as demonstrated in a co-culture system. The anti-PD-1/PD-L1 therapy enhanced T cell-mediated cytotoxicity of NSCLC cells treated with pemetrexed and expressing high levels of PD-L1 in comparison with untreated cells. These data may explain the positive results obtained with pemetrexed-based chemotherapy combined with pembrolizumab in PD-L1-negative NSCLC and can support pemetrexed as one of the preferable chemotherapy partners for immunochemotherapy combination regimens.

show abstract

Combined use of anti-ErbB monoclonal antibodies and erlotinib enhances antibody-dependent cellular cytotoxicity of wild-type erlotinib-sensitive NSCLC cell lines

Cited by 37 publications

References 36 publications

Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations

Modulating cancer cell mechanics and actin cytoskeleton structure by chemical and mechanical stimulations

Targeting the PI3K signaling pathway in KRAS mutant colon cancer

Pemetrexed Enhances Membrane PD-L1 Expression and Potentiates T Cell-Mediated Cytotoxicity by Anti-PD-L1 Antibody Therapy in Non-Small-Cell Lung Cancer

Contact Info

Product

Resources

About