Reversing microtubule‐directed chemotherapeutic drug resistance by co‐delivering α2β1 inhibitor and paclitaxel with nanoparticles in ovarian cancer

Zheng, Weihong; Ge, Dandi; Meng, Guohua

doi:10.1002/cbin.11261

Cited by 7 publications

(3 citation statements)

References 16 publications

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“…In addition, α2β1 integrin was shown to promote OC cell invasion by increasing matrix metalloproteinase (MMP)-2/MMP-9 activation, thereby disaggregating tumor cell spheroids and enhancing cell proliferation [ 20 ]. Integrin α2β1 was also shown to be involved in induction of chemoresistance in OC via phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway [ 21 ]. Su et al [ 22 ] isolated endothelial progenitor cells (EPCs) from OC patients, and demonstrated an increased integrin α4 expression, baseline migration, and adhesion mediated by the PI3K/AKT signaling pathway compared to those obtained from healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Krajnak

Jäkel

Anić

et al. 2021

Arch Gynecol Obstet

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Purpose Integrins may be involved in the metastatic spread of high-grade serous ovarian cancer (HGSOC) which determines the therapeutical approach and prognosis. We investigated the integrin expression in primary tumor and metastases of advanced HGSOC. Methods The expression of integrin α2, α4, α5, α6, and β1 was assessed by immunostaining in tumor samples of the ovary, omentum, and peritoneum of each patient. Differences in integrin expression among tumor localizations and their association with clinicopathological parameters were examined by Fisher’s exact test. The impact of integrin expression on progression-free survival (PFS) and overall survival (OS) was examined by Cox regression and Kaplan–Meier analyses. Results Hundred and thirteen tumor samples of 40 HGSOC patients were examined. The expression of the integrins did not differ between the three tumor localizations (all p values > 0.05) with the exception of high expression of integrin α4 in primary tumor and omentum (52.5% versus 47.5%, p = 0.008) and primary tumor and peritoneum (52.5% versus 47.5%, p = 0.050). High expression of integrin α4 in peritoneum was associated with poorer PFS (HR 2.02 95% CI 1.01–4.05, p = 0.047), younger age (p = 0.047), and death (p = 0.046). Median PFS in patients with high expression of integrin α4 was 13.00 months, whereas median PFS in patients without high expression of integrin α4 was 21.00 months (p = 0.040). Expression of other integrins did not correlate with PFS or OS. Conclusion Expression of integrin α4 may be altered during the metastatic spread of HGSOC and affect prognosis, whereas expression of integrin α2, α5, α6, and β1 did not reveal any prognostic value.

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Section: Discussionmentioning

confidence: 99%

Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Krajnak

Jäkel

Anić

et al. 2021

Arch Gynecol Obstet

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“…In the context of integrins, disease progression, and drug resistance in ovarian cancer, cell signaling pathways, including PI3K/Akt, Ras/Raf/MEK/ERK, Wnt, YAP/ TAZ, as well as crosstalk between integrins and the epidermal growth factor receptor (EGFR), have been most commonly investigated (Figure 2) [30][31][32][33][34][35]. A key player in the activation of the aforementioned pathways is focal adhesion kinase (FAK), a tyrosine kinase that localizes to focal adhesions [34,[36][37][38][39][40].…”

Section: Integrins In Ovarian Cancer and The Significance Of Ascites ...mentioning

confidence: 99%

“…The PI3K/ Akt pathway can also be activated by other cell surface receptors such as cytokine receptors and integrins. A recent study Zheng et al, found that α 2 β 1 overexpressing (α 2 β 1 + ) ovarian cancer cells, and ovarian cancer patient tissue samples that were resistant to microtubule-directed chemotherapeutic drugs, including paclitaxel and vincristine, had enhanced PI3K and Akt phosphorylation, as well as Akt translocation into the nucleus [30]. This suggests that α 2 β 1 integrins activate the PI3K/AKT pathway to promote resistance to microtubule-directed chemotherapeutic drugs.…”

Section: Pi3k/akt Pathwaymentioning

confidence: 99%

Integrins in Ovarian Cancer: Survival Pathways, Malignant Ascites and Targeted Photochemistry

Ruhi¹,

Rickard²,

Polacheck³

et al. 2023

Recent Advances, New Perspectives and Applications in the Treatment of Ovarian Cancer

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Integrins are surface adhesion molecules that, upon binding to ligands, cluster to form adhesion complexes. These adhesion complexes are comprised of structural and regulatory proteins that modulate a variety of cellular behaviors including differentiation, growth, and migration through bidirectional signaling activities. Aberrant integrin expression and activation in ovarian cancer plays a key role in the detachment of cancer cells from primary sites as well as migration, invasion, and spheroid formation. An emerging area is the activation or rearrangement of integrins due to mechanical stress in the tumor microenvironment, particularly in response to fluid shear stress imparted by currents of malignant ascites. This chapter describes the role of integrins in ovarian cancer with an emphasis on crosstalk with survival pathways, the effect of malignant ascites, and discusses the literature on integrin-targeting approaches in ovarian cancer, including targeted photochemistry for therapy and imaging.

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DMBT1 suppresses cell proliferation, migration and invasion in ovarian cancer and enhances sensitivity to cisplatin through galectin‐3/PI3k/Akt pathway

Zhao

2020

Cell Biochemistry & Function

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Ovarian cancer (OC) is one of the most common gynaecologic malignancies. Deleted in malignant brain tumors 1 (DMBT1) was considered as a tumour suppressor in multiple cancers, but there have been no systemic profiling studies of DMBT1 in OC until now. The aim of this study is to explore the role and the potential mechanism of DMBT1 in OC. mRNA levels and protein expressions of corresponding genes were detected by quantitative real‐time polymerase chain reaction and western blot. Cell proliferation was detected by CCK‐8 assay and cell colony formation. Cell migration and invasion were detected by wound healing and transwell assay. The combination between DMBT1 and galectin‐3 was demonstrated by immunoprecipitation. We demonstrated that DMBT1 was downregulated in OC cell lines, especially SKOV3 cells. Overexpression of DMBT1 significantly inhibited cell proliferation, colony formation, migration and invasion, as well as decreased Matrix Metalloproteinase‐2 (MMP‐2) and MMP‐7. DMBT1 caused a reduction of cell viability by treatment with cisplatin. Immunoprecipitation assay revealed a combination between DMBT1 and galectin‐3. DMBT1 could decrease the expression of galectin‐3 and inhibit the phosphorylation of PI3K and AKT, while overexpression of galectin‐3 reversed this effect. In summary, DMBT1 might inhibit the progression of OC and improve the sensitivity of SKOV3 cells to cisplatin through galectin‐3/PI3K/AKT pathway, giving a new insight into the role of DMBT1 in OC and enriching the potential strategies for OC treatment.Significance of the StudyThe present study focus on the role and the potential mechanism of DMBT1 in ovarian cancer (OC). We demonstrated that DMBT1 might inhibit the progression of ovarian by inhibiting cell proliferation, migration and invasion and increased the sensitivity to cisplatin through galectin‐3/PI3K/AKT pathway. The findings ensure the interaction relation between DMBT1 and galectin‐3 in OC, providing a novel biological marker for OC and enriching the potential strategies for OC treatment.

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Reversing microtubule‐directed chemotherapeutic drug resistance by co‐delivering α2β1 inhibitor and paclitaxel with nanoparticles in ovarian cancer

Cited by 7 publications

References 16 publications

Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Integrins in Ovarian Cancer: Survival Pathways, Malignant Ascites and Targeted Photochemistry

DMBT1 suppresses cell proliferation, migration and invasion in ovarian cancer and enhances sensitivity to cisplatin through galectin‐3/PI3k/Akt pathway

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