scholarly journals Prognostic and Therapeutic Utility of Variably Expressed Cell Surface Receptors in Osteosarcoma

Sarcoma ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yoav Zvi ◽  
Elif Ugur ◽  
Brian Batko ◽  
Jonathan Gill ◽  
Michael Roth ◽  
...  
Keyword(s):  
Overall Survival ◽  
Growth Factor ◽  
Cell Surface ◽  
Cell Lines ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Cell Surface Receptors ◽  
Surface Receptors ◽  
Variable Expression ◽  
Her 2

Background. Six cell surface receptors, human epidermal growth factor receptor-2 (Her-2), platelet-derived growth factor receptor-β (PDGFR-β), insulin-like growth factor-1 receptor (IGF-1R), insulin receptor (IR), c-Met, and vascular endothelial growth factor receptor-3 (VEGFR-3), previously demonstrated variable expression across varying patient-derived and standard osteosarcoma (OS) cell lines. The current study sought to validate previous expression patterns and evaluate whether these receptors offer prognostic and/or therapeutic value. Methods. Patient-derived OS cell lines (n = 52) were labeled with antibodies to Her-2, PDGFR-β, IGF-1R, IR, c-Met, and VEGFR-3. Expression was characterized using flow cytometry. The difference in geometric mean fluorescent intensity (geoMFIdiff = geoMFIpositive − geoMFInegative) was calculated for each receptor across all cell lines. Receptor expression was categorized as low (Q1), intermediate (Q2, Q3), or high (Q4). The event-free survival (EFS) and overall survival for the six cell surface receptors were estimated by the Kaplan–Meier method. Differences in hazard for EFS event and overall survival event for patients in each of the three expression levels in each of the six cell surface receptors were assessed using the log-rank test. Results. All 6 receptors were variably expressed in the majority of cell lines. IR and PDGFR-β expressions were found to be significant predictors for EFS amongst patients with nonmetastatic disease ( p = 0.02 and 0.01, respectively). The hazard ratio for EFS was significantly higher between high IR and intermediate IR expression (HR = 2.66, p = 0.02 ), as well as between high PDGFR-β and intermediate PDGFR-β expression (HR = 5.68, p = 0.002 ). Her-2, c-Met, IGF-1R, and VEGFR-3 were not found to be significant predictors for either EFS or overall survival. Conclusion. The six cell surface receptors demonstrated variable expression across the majority of patient-derived OS cell lines tested. Limited prognostic value was offered by IR and PDGFR-β expression within nonmetastatic patients. The remaining receptors do not provide clear prognostic utility. Nevertheless, their consistent, albeit variable, surface expression across a large panel of patient-derived OS cell lines maintains their potential use as future therapeutic targets.

scholarly journals Expression of a type I insulin-like growth factor receptor with low affinity for insulin-like growth factor II

1992 ◽  
Vol 281 (2) ◽  
pp. 413-417 ◽  
Author(s):  
E L Germain-Lee ◽  
M Janicot ◽  
R Lammers ◽  
A Ullrich ◽  
S J Casella
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Growth Factor Receptor ◽  
Cell Surface Receptors ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Surface Receptors ◽  
3T3 Fibroblasts ◽  
Igf I ◽  
Nih 3T3

We investigated the binding properties of the type I insulin-like growth factor (IGF) receptor expressed in NIH-3T3 fibroblasts transfected with a human type I receptor cDNA. Cell surface receptors bound IGF-I with KD = 1 nM as predicted. Although recent studies have suggested that IGF-I and IGF-II bind to type I receptors with near-equal affinity, the receptors in this system bound IGF-II with much lower affinity (KD = 15-20 nM). When type I receptors from the transfected cells were solubilized and immunopurified, however, both 125I-IGF-I and 125I-IGF-II bound to the purified receptors with extremely high and relatively similar affinities (KD = 8 and 17 pM respectively). Thus the immunopurified receptors had higher affinity but lower specificity for the two ligands. The monoclonal antibody alpha IR-3 effectively inhibited IGF-I binding to cell surface receptors (75 +/- 10%), but did not inhibit IGF-II binding. In the purified receptor assay, alpha IR-3 also inhibited IGF-I binding more effectively than IGF-II binding (38 +/- 7% versus 10 +/- 4%). We conclude that the products of this cDNA can account for the binding patterns that we previously observed in receptors immunopurified from human placenta. The differential effect of alpha IR-3 on IGF-I versus IGF-II raises the possibility that these homologous growth factors bind to immunologically distinct epitopes on the type I receptor.

Effectiveness and safety of eribulin for human epidermal growth factor receptor 2 negative metastatic breast cancer in a real-world population

2021 ◽  
pp. 107815522110382
Author(s):  
Rocío Díaz-Acedo ◽  
Silvia Artacho Criado ◽  
Rocío Jiménez Galán ◽  
Antonio Gutiérrez Pizarraya ◽  
Mercedes Galván Banqueri ◽  
...  
Keyword(s):  
Overall Survival ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Confidence Interval ◽  
Median Overall Survival ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Human Epidermal Growth Factor ◽  
Epidermal Growth

Background Eribulin’s clinical benefit remains unclear; so, studies analyzing its effectiveness in routine clinical practice are interesting. Patients and methods This is a multicenter, retrospective study including patients with human epidermal growth factor receptor-2-negative metastatic breast cancer which assesses effectiveness and safety of eribulin. Results A total of 140 women were included, with a median age of 57 years. The median overall survival and progression-free survival were 8.8 (95% confidence interval: 6.1–11.4) and 2.8 months (95% confidence interval: 2.5–3.1), respectively. For patients with hormonal receptor expression, a significantly longer progression-free survival was observed: 3.4 (95%confidence interval: 2.3–4.5) versus triple negative: 2.0 (95%confidence interval: 1.7–2.3) months, p = 0.003. Also, those who had received capecitabine prior to eribulin had a higher median overall survival than those who had not received it (9.5 months, 95% confidence interval: 6.6–12.5 vs. 4.8 months, 95% confidence interval: 3.4–6.2; p = 0.001). When only triple-negative patients were included, median overall survival was 6.5 (95% confidence interval: 0.1–16.2) for those who had received previous capecitabine versus 4.3 (95% confidence interval: 2.8–5.8) months for patients who had not received it; p =0.006. The safety profile of eribulin was adequate. Conclusion Effectiveness of eribulin in a real-life human epidermal growth factor receptor-2--negative population is lower than that observed in clinical trials. Its benefit seems to be higher in patients with hormonal receptor expression and patients who had received capecitabine prior to eribulin. The safety profile of eribulin is adequate.

scholarly journals Vav Family Proteins Couple to Diverse Cell Surface Receptors

2000 ◽  
Vol 20 (17) ◽  
pp. 6364-6373 ◽  
Author(s):  
Sheri L. Moores ◽  
Laura M. Selfors ◽  
Jessica Fredericks ◽  
Timo Breit ◽  
Keiko Fujikawa ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Surface ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinases ◽  
Protein Tyrosine Kinase ◽  
Receptor Activation ◽  
Cell Surface Receptors ◽  
Nucleotide Exchange ◽  
Surface Receptors ◽  
Downstream Signaling

ABSTRACT Vav proteins are guanine nucleotide exchange factors for Rho family GTPases which activate pathways leading to actin cytoskeletal rearrangements and transcriptional alterations. Vav proteins contain several protein binding domains which can link cell surface receptors to downstream signaling proteins. Vav1 is expressed exclusively in hematopoietic cells and tyrosine phosphorylated in response to activation of multiple cell surface receptors. However, it is not known whether the recently identified isoforms Vav2 and Vav3, which are broadly expressed, can couple with similar classes of receptors, nor is it known whether all Vav isoforms possess identical functional activities. We expressed Vav1, Vav2, and Vav3 at equivalent levels to directly compare the responses of the Vav proteins to receptor activation. Although each Vav isoform was tyrosine phosphorylated upon activation of representative receptor tyrosine kinases, integrin, and lymphocyte antigen receptors, we found unique aspects of Vav protein coupling in each receptor pathway. Each Vav protein coprecipitated with activated epidermal growth factor and platelet-derived growth factor (PDGF) receptors, and multiple phosphorylated tyrosine residues on the PDGF receptor were able to mediate Vav2 tyrosine phosphorylation. Integrin-induced tyrosine phosphorylation of Vav proteins was not detected in nonhematopoietic cells unless the protein tyrosine kinase Syk was also expressed, suggesting that integrin activation of Vav proteins may be restricted to cell types that express particular tyrosine kinases. In addition, we found that Vav1, but not Vav2 or Vav3, can efficiently cooperate with T-cell receptor signaling to enhance NFAT-dependent transcription, while Vav1 and Vav3, but not Vav2, can enhance NFκB-dependent transcription. Thus, although each Vav isoform can respond to similar cell surface receptors, there are isoform-specific differences in their activation of downstream signaling pathways.

Preliminary evaluation of HER-2/neu oncogene and epidermal growth factor receptor expression in normal and neoplastic human ovaries

1992 ◽  
Vol 7 (2) ◽  
pp. 114-118 ◽  
Author(s):  
A.M. Mileo ◽  
M. Fanuele ◽  
F. Battaglia ◽  
G. Scambia ◽  
C. Benedetti-Panici ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Preliminary Evaluation ◽  
Apparent Difference ◽  
Her 2 ◽  
Epidermal Growth ◽  
Neu Oncogene

The HER-2/neu oncogene (a member of the Erb-like oncogene family) is distinct from but closely related to the c-erb B gene which encodes the epidermal growth factor receptor (EGFr). HER-2/neu gene amplification was found in a large number of mammary carcinomas and there was a strong correlation between this phenomenon and poor prognosis. In our study HER-2/neu oncogene expression was determined in 16 malignant ovarian tumors, 2 ovarian lymphomas and 5 normal ovaries. The HER-2/neu gene was found both in normal ovaries and malignant tumors, without any apparent difference among the various histological types. In all the specimens examined, HER-2/neu expression did not seem to be related to EGF binding capacity.

scholarly journals Regulation of cell-surface receptors for human interferon-γ on the human histiocytic lymphoma cell line U937

1991 ◽  
Vol 274 (3) ◽  
pp. 775-780 ◽  
Author(s):  
D S Finbloom
Keyword(s):  
Cell Surface ◽  
Cell Line ◽  
Specific Radioactivity ◽  
Receptor Expression ◽  
Cell Surface Expression ◽  
Cell Surface Receptors ◽  
Minor Role ◽  
Ifn Gamma ◽  
Surface Receptors ◽  
High Specific Radioactivity

Interferon-gamma (IFN gamma) binds to high-affinity receptors on monocytes and is rapidly internalized. This study investigates the ability of the human monocyte-like cell line, U937, to regulate the cell-surface expression of the IFN gamma receptor (IFN gamma R) during endocytosis of ligand. Recombinant IFN gamma was radiolabelled to high specific radioactivity with Bolton-Hunter reagent and used to enumerate IFN gamma R on treated U937 cells. Cells which had internalized IFN gamma for up to 3 h displayed maximal levels of IFN gamma R at all time points tested after all unlabelled IFN gamma had been acid-stripped from the cell at pH 2.78. Therefore there was no evidence of down-modulation of the receptor. After trypsin treatment of the IFN gamma R, the cells were able to synthesize and insert into the cell membrane up to 1000 IFN gamma R molecules/h after a 60 min lag. Since biosynthesis played a minor role during the first 30 min of endocytosis, I examined other possibilities to explain the lack of down-modulation of the receptor. A solubilized-receptor assay revealed the presence of an intracellular pool of receptors equal to about 25% of the number of cell surface receptors. Using trypsin to differentiate between intracellular and surface receptors, I observed that 43% of those receptors that were internalized after a 30 min exposure to IFN gamma (580 molecules) could be recycled back to the plasma membrane. In addition, equal rates of receptor decay (t1/2 = 5 h) were observed in the presence of cycloheximide with or without IFN gamma. All the data taken together suggest that during the first 30 min of endocytosis both the expression of an intracellular source of receptor and recycling of internalized receptors contribute to maintain optimal receptor expression.

scholarly journals Expression and clinical significance of the receptors of the EGF family in oral squamous cell carcinomas

2019 ◽  
Vol 4 ◽  
pp. 2057178X1983653
Author(s):  
Upul Dissanayake
Keyword(s):  
Overall Survival ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Growth Factor ◽  
Squamous Cell ◽  
Logistic Regression Analysis ◽  
Growth Factor Receptor ◽  
Squamous Cell Carcinomas ◽  
Her 2

Objective: To examine the immunohistochemical expression of four members of the type 1 growth factor receptor family in oral squamous cell carcinomas (OSCCs) and to correlate with clinical outcomes. Materials and methods: Sixty OSCCs from a patient cohort in Sri Lanka were included in the study. Five sections from each carcinoma were immunostained with antibodies to epidermal growth factor receptor (EGFR)/c-erbB-1, c-erbB-2/HER-2/neu, c-erbB-3/HER-3 and c-erbB-4/HER-4. Two clones were used to stain for c-erbB-2/HER-2/neu. Semiquantitative analysis of immunoreactivity was carried out by scoring the intensity of expression and proportions of positively stained cells. A logistic regression analysis was performed to examine positive expression against overall survival. Results: There was heterogenous expression of the four receptors, positivity ranging from 26% to 60%. Co-expression of all four markers was observed only in 1–3% of the tumours. Both membranous and cytoplasmic expressions were observed, EGFR showing predominantly membranous expression and c-erbB-2 showing only cytoplasmic staining. In logistic regression analysis, none of the growth factor receptors were significantly predictive of overall survival. Conclusion: Type 1 growth factor receptors are highly expressed in oral carcinomas, EGFR being the predominant marker.

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