In vivo tumor growth of high-grade serous ovarian cancer cell lines

Mitra, Anirban; Davis, David A.; Tomar, Sunil; Roy, Lynn; Gurler, Hilal; Xie, Jia; Lantvit, Daniel D.; Cárdenas, Horacio; Fang, Fang; Liu, Yueying; Loughran, Elizabeth A.; Yang, Jing; Stack, M. Sharon; Emerson, Robert E.; Dahl, Karen D. Cowden; Barbolina, Maria V.; Nephew, Kenneth P.; Matei, Daniela; Burdette, Joanna E.

doi:10.1016/j.ygyno.2015.05.040

Cited by 166 publications

(172 citation statements)

References 22 publications

Supporting

Mentioning

154

Contrasting

Order By: Relevance

“…Consistent with previous reports, 13 we found that subcutaneous OVCAR-4 tumors grew slowly, but reliably in nude mice. Fluorescence imaging of the excised tumors from mice treated with fluorescent probe showed the same trend as the cell internalization studies.…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

High expression of integrin αvβ3 enables uptake of targeted fluorescent probes into ovarian cancer cells and tumors

Shaw

Schreiber

Roland

et al. 2018

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 93%

“…A recent in vivo study demonstrated the ability of this cell line to reliably form xenograft tumors in nude mice, suggesting that it as a promising experimental model for the ovarian cancer community. 13 However, the susceptibility of OVCAR-4 cells to the more common types of molecular targeting is not known. 14 …”

Section: Introductionmentioning

confidence: 99%

High expression of integrin αvβ3 enables uptake of targeted fluorescent probes into ovarian cancer cells and tumors

Shaw

Schreiber

Roland

et al. 2018

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

“…To determine TG2 expression in OCSCs, we used Q-RT-PCR and compared ALDH + /CD133 + and ALDH − /CD133 − cells FACS sorted from OVCAR5 and COV362, two representative HGSOC cell lines (25,26). TG2 m RNA expression was significantly increased in OCSCs compared to non-CSC (ALDH − /CD133 − Fig.…”

Section: Resultsmentioning

confidence: 99%

Tissue Tranglutaminase Regulates Interactions between Ovarian Cancer Stem Cells and the Tumor Niche

et al. 2018

Self Cite

View full text Add to dashboard Cite

Cancer progression and recurrence are linked to a rare population of cancer stem cells (CSC). Here we hypothesized that interactions with the extracellular matrix drive CSC proliferation and tumor-initiating capacity and investigated the functions of scaffold protein tissue transglutaminase (TG2) in ovarian CSC. Complexes formed by TG2, fibronectin (FN), and integrin β1 were enriched in ovarian CSC and detectable in tumors. A function-inhibiting antibody against the TG2 FN-binding domain suppressed complex formation, CSC proliferation as spheroids, tumor-initiating capacity, and stemness-associated Wnt/β-catenin signaling. Disruption of the interaction between TG2 and FN also blocked spheroid formation and the response to Wnt ligands. TG2 and the Wnt receptor Frizzled 7 (Fzd7) form a complex in cancer cells and tumors, leading to Wnt pathway activation. Protein docking and peptide inhibition demonstrate that the interaction between TG2 and Fzd7 overlaps with the FN binding domain of TG2. These results support a new function of TG2 in ovarian CSC, linked to spheroid proliferation and tumor-initiating capacity and mediated through direct interactions with Fzd7. We propose this complex as a new stem cell target.

show abstract

“…PARP1 was deleted in UWB1.289 and OVCAR8 EOC cell lines that have reduced BRCA-1 expression through a deleterious mutation (UWB1.289) or promoter methylation (OVCAR8). These mutations are characterized elsewhere in the literature (46,47 radiography studies and analyzed data. HW designed CRISPR/ Cas9 guides for PARP-1 and performed in vitro PARP1-KO experiments.…”

Section: Methodsmentioning

confidence: 99%

A PET imaging agent for evaluating PARP-1 expression in ovarian cancer

Makvandi

Pantel

Schwartz

et al. 2018

Journal of Clinical Investigation

106

107

View full text Add to dashboard Cite

50% of patients with HRD respond to PARPi therapy (3). Moreover, patients without known HRD have also shown a clinical benefit from PARPis, as seen in recent trials assessing niraparib, olaparib, or rucaparib, as maintenance therapy in platinum-sensitive recurrent ovarian cancer (5-8). Given that not all patients will respond to PARPi therapy, improved clinical tools for predicting which patients will respond are urgently needed.Numerous clinical trials have led to FDA approval of 3 PARPis since 2014 and there is continued development of 2 additional drugs within this class (9-13). Despite growth in the BACKGROUND. Poly(ADP-ribose) polymerase (PARP) inhibitors are effective in a broad population of patients with ovarian cancer; however, resistance caused by low enzyme expression of the drug target PARP-1 remains to be clinically evaluated in this context. We hypothesize that PARP-1 expression is variable in ovarian cancer and can be quantified in primary and metastatic disease using a novel PET imaging agent. METHODS.We used a translational approach to describe the significance of PET imaging of PARP-1 in ovarian cancer. First, we produced PARP1-KO ovarian cancer cell lines using CRISPR/Cas9 gene editing to test the loss of PARP-1 as a resistance mechanism to all clinically used PARP inhibitors. Next, we performed preclinical microPET imaging studies using ovarian cancer patient-derived xenografts in mouse models. Finally, in a phase I PET imaging clinical trial we explored PET imaging as a regional marker of PARP-1 expression in primary and metastatic disease through correlative tissue histology. RESULTS.We found that deletion of PARP1 causes resistance to all PARP inhibitors in vitro, and microPET imaging provides proof of concept as an approach to quantify PARP-1 in vivo. Clinically, we observed a spectrum of standard uptake values (SUVs) ranging from 2-12 for PARP-1 in tumors. In addition, we found a positive correlation between PET SUVs and fluorescent immunohistochemistry for PARP-1 (r 2 = 0.60).CONCLUSION. This work confirms the translational potential of a PARP-1 PET imaging agent and supports future clinical trials to test PARP-1 expression as a method to stratify patients for PARP inhibitor therapy.TRIAL REGISTRATION. Clinicaltrials.gov NCT02637934. 22-24). Furthermore, PARP-1 has been development and application of PARPis, the primary drug target poly(ADP-ribose) polymerase 1 (PARP-1) has never been evaluated in vivo, even though loss of expression in vitro is a wellcharacterized resistance mechanism (3,(14)(15)(16)(17)(18)(19). It was first hypothesized that PARPis work primarily through a synthetic lethality pathway where loss of BRCA1 or BRCA2 combined with chemical inhibition of PARP-1 results in cell death (20, 21). However, it was later shown that deletion of PARP1 did not result in BRCA1-restored cells showed no increase in γH2AX compared with DMSO controls. Olaparib-treated OVCAR8 PARP1-KO G1 and G3 cells showed a 1.3 times increase (ANOVA, **P < 0.01 and ***P < 0.001, respectively) in γH2AX...

show abstract

In vivo tumor growth of high-grade serous ovarian cancer cell lines

Cited by 166 publications

References 22 publications

High expression of integrin αvβ3 enables uptake of targeted fluorescent probes into ovarian cancer cells and tumors

High expression of integrin αvβ3 enables uptake of targeted fluorescent probes into ovarian cancer cells and tumors

Tissue Tranglutaminase Regulates Interactions between Ovarian Cancer Stem Cells and the Tumor Niche

A PET imaging agent for evaluating PARP-1 expression in ovarian cancer

Contact Info

Product

Resources

About