Engagement of Integrinβ1 Induces Resistance of Bladder Cancer Cells to Mitomycin-C

Zhang, Chengjing; Zhang, Shen; Pan, Chun-Wu; Zhong, Shan; Li, Tao; Zhang, Minguang

doi:10.1016/j.urology.2011.12.012

Cited by 12 publications

(15 citation statements)

References 22 publications

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“…Interestingly, Zhang and coworkers showed that they could reverse chemoresistance to mitomycin c by blocking integrin β1 (4). Integrin β1 was overexpressed in most of the tested sublines and it was reported to contribute to a more malignant phenotype in urothelial bladder cancer (4,25). We could confirm in this study that overexpression of integrin β1 is associated with a malignant phenotype since we detected a stronger expression in malignant tissue samples compared to normal urothelium.…”

Section: Discussionsupporting

confidence: 73%

“…Since chemotaxis was frequently enhanced after acquisition of resistance, these results might support the conclusions of Chakraborty et al (25) who postulated that blockade of β1-integrin with a specific antibody could result in alteration of multiple signaling pathways related to adhesion and migration. Interestingly, Zhang and coworkers showed that they could reverse chemoresistance to mitomycin c by blocking integrin β1 (4). Integrin β1 was overexpressed in most of the tested sublines and it was reported to contribute to a more malignant phenotype in urothelial bladder cancer (4,25).…”

Section: Discussionmentioning

confidence: 99%

“…Integrins have been identified to play an important role in the development of resistance to chemotherapy in bladder cancer (4). These molecules are transmembrane receptors with two different chains, an α (alpha) and a β (beta) subunit.…”

Section: Introductionmentioning

confidence: 99%

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Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

et al. 2017

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Abstract. Treatment failure in metastatic bladder cancer is commonly caused by acquisition of resistance to chemotherapy in association with tumor progression. Since alterations of integrins can influence the adhesive and invasive behaviors of urothelial bladder cancer cell lines, the present study aimed to evaluate the role of integrins in bladder cancer cells with acquired resistance to standard first-line chemotherapy with gemcitabine, and cisplatin. Therefore, four gemcitabineand four cisplatin-resistant sublines out of a panel of four parental urothelial bladder cancer cell lines (TCC-SUP, HT1376, T24, and 5637) were used. Expression of integrin subunits α3, α5, α6, β1, β3, and β4 was detected using flow cytometry. Adhesion and chemotaxis were analyzed. For functional assays, integrin β1 was attenuated with a blocking antibody. In untreated cells, chemotaxis was upregulated in 3/4 gemcitabine-resistant sublines. In cisplatin-resistant cells, chemotaxis was enhanced in 2/4 cell lines. Acquired chemoresistance induced the upregulation of integrin β1 in all four tested gemcitabine-resistant sublines, as well as an upregulation in 3/4 cisplatin-resistant sublines compared with parental cell lines. Following the inhibition of integrin β1, adhesion to extracellular matrix components was downregulated in 3/4 gemcitabine-resistant sublines and in all four tested cisplatin-resistant sublines. Since integrin β1 is frequently upregulated in chemoresistant urothelial cancer cell lines and inhibition of integrin β1 may influence adhesion, further studies are warranted to evaluate integrin β1 as a potential therapeutic target for bladder cancer in vivo.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionmentioning

confidence: 99%

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Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

et al. 2017

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“…Drug resistance can either be an innate property (intrinsic resistance) due to rare genetic changes or be acquired during chemotherapy (extrinsic resistance) [27]. Several in vitro studies have implicated the integrin β 1 subunit in the development of resistance towards different chemotherapeutic compounds in various cancers, including solid tumors of the breast [28,29,30,31,32], bladder [33], prostate [34,35], lungs (small cell and non-small cell lung cancer) [36,37,38], and pancreas [39,40], as well as hematological malignancies, such as multiple myeloma, myeloid and B lymphoid malignancies [41,42]. In addition, clinical studies have shown an association between increased integrin β 1 expression and decreased survival and poor prognosis in patients with invasive breast cancer and small cell lung carcinoma [43,44].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, clinical studies have shown an association between increased integrin β 1 expression and decreased survival and poor prognosis in patients with invasive breast cancer and small cell lung carcinoma [43,44]. Furthermore, inhibition of integrin β 1 reduces chemoresistance in bladder cancer [33] and enhances the sensitivity to radiation treatment in human breast cancer xenografts [45]. The integrin β 1 -mediated tumor cell survival and chemoresistance appear to be facilitated by adhesion to integrin β 1 ligands, including fibronectin, collagens, and laminin, causing the activation of downstream signaling molecules, where PI3K and Akt play major roles [5].…”

Section: Introductionmentioning

confidence: 99%

Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells

Sørensen

Rasmussen

Broberg

et al. 2015

Cell Physiol Biochem

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Background/Aims:Altered expression of the integrin family of cell adhesion receptors has been associated with initiation, progression, and metastasis of solid tumors as well as in the development of chemoresistance. Here, we investigated the role of integrins, in particular integrin β₁, in cell volume regulation and drug-induced apoptosis in adherent and non-adherent Ehrlich ascites cell lines. Methods:Adhesion phenotypes were verified by colorimetric cell-adhesion-assay. Quantitative real-time PCR and western blot were used to compare expression levels of integrin subunits. Small interfering RNA was used to silence integrin β₁ expression. Regulatory volume decrease (RVD) after cell swelling was studied with calcein-fluorescence-self-quenching and Coulter counter analysis. Taurine efflux was estimated with tracer technique. Caspase assay was used to determine apoptosis. Results:We show that adherent cells have stronger fibronectin binding and a significantly increased expression of integrin α₅, α_v, and β₁ at mRNA and protein level, compared to non-adherent cells. Knockdown of integrin β₁ reduced RVD of the adherent but not of the non-adherent cells. Efflux of taurine was unaffected. In contrast to non-adherent, adherent cells exhibited chemoresistance to chemotherapeutic drugs (cisplatin and gemcitabine). However, knockdown of integrin β₁ promoted cisplatin-induced caspase activity in adherent cells. Conclusion:Our data identifies integrin β₁ as a part of the osmosensing machinery and regulator of cisplatin resistance in adherent Ehrlich cells.

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Shielding and nurturing: Fibronectin as a modulator of cancer drug resistance

Farooq

Amin

Wani

et al. 2023

Journal Cellular Physiology

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Resistance to chemotherapy and targeted therapies constitute a common hallmark of most cancers and represent a dominant factor fostering tumor relapse and metastasis. Fibronectin, an abundant extracellular matrix glycoprotein, has long been proposed to play an important role in the pathobiology of cancer. Recent research has unraveled the role of Fibronectin in the onset of chemoresistance against a variety of antineoplastic drugs including DNA‐damaging agents, hormone receptor antagonists, tyrosine kinase inhibitors, microtubule destabilizing agents, etc. The current review summarizes the role played by Fibronectin in mediating drug resistance against diverse anticancer drugs. We have also discussed how the aberrant expression of Fibronectin drives the oncogenic signaling pathways ultimately leading to drug resistance through the inhibition of apoptosis, promotion of cancer cell growth and proliferation.

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Engagement of Integrinβ1 Induces Resistance of Bladder Cancer Cells to Mitomycin-C

Cited by 12 publications

References 22 publications

Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

Blocking integrin β1 decreases adhesion in chemoresistant urothelial cancer cell lines

Integrin β1, Osmosensing, and Chemoresistance in Mouse Ehrlich Carcinoma Cells

Shielding and nurturing: Fibronectin as a modulator of cancer drug resistance

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