Quantitative assessment of breast cancer liver metastasis expansion with patient-derived xenografts

Alzubi, Mohammad A.; Sohal, Sahib S.; Sriram, M; Turner, Tia H.; Zot, Patricija; Idowu, Michael O.; Harrell, J. Chuck

doi:10.1007/s10585-019-09968-z

Cited by 9 publications

(8 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, our current findings of the cell clustering in the stromal compartment of the LS-ECM are consistent with the detection of non-vascularized hepatic metastases presented as cellular clumps via Doppler sonography near the liver portal triads [ 114 ]. The observed pattern of TNBC cell compartment-specific distribution across the LS-ECM also explains the negligible detectability [ 17 , 115 , 116 , 117 ] of single-cell occult metastases in the liver parenchyma vs. the cell clusters near blood vessels and other stromal components. Then, an enhanced detection sensitivity is needed to reveal the micrometastases hidden in the liver parenchyma.…”

Section: Discussionmentioning

confidence: 98%

Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications

et al. 2021

View full text Add to dashboard Cite

Colonization of distant organs by tumor cells is a critical step of cancer progression. The initial avascular stage of this process (micrometastasis) remains almost inaccessible to study due to the lack of relevant experimental approaches. Herein, we introduce an in vitro/in vivo model of organ-specific micrometastases of triple-negative breast cancer (TNBC) that is fully implemented in a cost-efficient chick embryo (CE) experimental platform. The model was built as three-dimensional (3D) tissue engineering constructs (TECs) combining human MDA-MB-231 cells and decellularized CE organ-specific scaffolds. TNBC cells colonized CE organ-specific scaffolds in 2–3 weeks, forming tissue-like structures. The feasibility of this methodology for basic cancer research, drug development, and nanomedicine was demonstrated on a model of hepatic micrometastasis of TNBC. We revealed that MDA-MB-231 differentially colonize parenchymal and stromal compartments of the liver-specific extracellular matrix (LS-ECM) and become more resistant to the treatment with molecular doxorubicin (Dox) and Dox-loaded mesoporous silica nanoparticles than in monolayer cultures. When grafted on CE chorioallantoic membrane, LS-ECM-based TECs induced angiogenic switch. These findings may have important implications for the diagnosis and treatment of TNBC. The methodology established here is scalable and adaptable for pharmacological testing and cancer biology research of various metastatic and primary tumors.

show abstract

Section: Discussionmentioning

confidence: 98%

Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Median OS (months (95% CI)) for desmoplastic versus non-desmoplastic patient cohorts is 88 versus 53 (49)(50)(51)(52)(53)(54)(55)(56)(57)(58) months, respectively. Median DFS for desmoplastic versus nondesmoplastic patient cohorts is 24 (20-33) versus 11 (11)(12) months, respectively (Figures 2A and 2B, Table 4). The adjusted HRs for OS and DFS (95% CI) are 0.64 (0.52-0.78) and 0.61 (0.52-0.71), respectively (Table 4).…”

Section: Update Of the Cut-off Value To Categorize Patients With Colo...mentioning

confidence: 99%

“…In addition, attempts have been made to develop technologies for predicting HGPs using medical imaging and machinelearning algorithms [7][8][9][10] . Novel animal models for liver metastasis exhibiting features of the different HGPs are a particularly valuable development [11][12][13][14][15][16][17] . These models will allow us to: 1) perform functional validation of HGP-specific signalling pathways described in the clinical samples of liver metastases, 2) identify non-invasive surrogate markers for the different HGPs and 3) test the efficacy of new therapeutic strategies based on the HGPs.…”

Section: Introductionmentioning

confidence: 99%

Histopathological growth patterns of liver metastasis: updated consensus guidelines for pattern scoring, perspectives, and recent mechanistic insights

Latacz

Höppener

Bohlok

et al. 2022

Preprint

View full text Add to dashboard Cite

The first consensus guidelines for scoring the histopathological growth patterns (HGPs) of liver metastases were established in 2017. Since then, numerous studies have applied these guidelines, have further substantiated the potential clinical value of the HGPs in patients with liver metastases from various tumour types and are starting to shed light on the biology of the distinct HGPs. In the present guidelines, we give an overview of these studies, discuss novel strategies for predicting the HGPs of liver metastases, such as deep learning algorithms for whole slide histopathology images and medical imaging, and highlight liver metastasis animal models that exhibit features of the different HGPs. Based on a pooled analysis of large cohorts of patients with liver-metastatic colorectal cancer, we propose a new cut-off to categorise patients according to the HGPs. An up-to-date standard method for HGP assessment within liver metastases is also presented with the aim of incorporating HGPs into the decision-making processes surrounding the treatment of patients with liver metastatic cancer. Finally, we propose hypotheses on the cellular and molecular mechanisms that drive the biology of the different HGPs, opening some exciting pre-clinical and clinical research perspectives.

show abstract

“…Therefore, the efficacy of Triplatin was compared in TNBC PDX with high and low levels of sGAGs to test the hypothesis that PDX models with high levels of sGAG staining will be most responsive to Triplatin. We examined 3 PDX TNBC models, previously investigated for sensitivity to carboplatin -UCD52 (carboplatin-sensitive), WHIM30 (carboplatin-sensitive) and WHIM2 (carboplatin-resistant) (36)(37)(38)(39). WHIM30 and WHIM2 had significantly higher sGAG levels compared to UCD52 (Fig 5A -B).…”

Section: Triplatin Has Reduced Accumulation In Sgag Deficient Tnbc Cells and Inhibits Primary Tumor Growth And Metastasis In Carboplatin mentioning

confidence: 99%

Exploitation of sulfated glycosaminoglycan status for precision medicine of platinums in triple-negative breast cancer

Hampton

Peterson

Katner

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

Triple negative breast cancer (TNBC) is a subtype of breast cancer lacking targetable biomarkers. TNBC is known to be most aggressive, and when metastatic is often drug resistant and uncurable. Biomarkers predicting response to therapy improve treatment decisions and allow personalized approaches for TNBC patients. This study explores sulfated glycosaminoglycan (sGAG) levels as a predictor of TNBC response to platinum therapy. sGAG levels were quantified in three distinct TNBC tumor models including cell line-derived, patient-derived xenograft (PDX) tumors, and isogenic models deficient in sGAG biosynthesis. The in vivo antitumor efficacy of Triplatin, a sGAG-directed platinum agent, was compared in these models to the clinical platinum agent, carboplatin. We determined that >40% of TNBC PDX tissue microarray samples have high levels of sGAGs. The in vivo accumulation of Triplatin in tumors as well as antitumor efficacy of Triplatin positively correlated with sGAG levels on tumor cells, whereas carboplatin followed the opposite trend. In carboplatin-resistant tumor models expressing high levels of sGAGs, Triplatin decreased primary tumor growth, reduced lung metastases and inhibited metastatic growth in lungs, liver, and ovaries. sGAG levels served as a predictor of Triplatin sensitivity in TNBC. Triplatin may be particularly beneficial in treating patients with chemotherapy-resistant tumors who have evidence of residual disease after standard neoadjuvant chemotherapy. More effective neoadjuvant and adjuvant treatment will likely improve clinical outcome of TNBC.

show abstract

Quantitative assessment of breast cancer liver metastasis expansion with patient-derived xenografts

Cited by 9 publications

References 36 publications

Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications

Chick Embryo Experimental Platform for Micrometastases Research in a 3D Tissue Engineering Model: Cancer Biology, Drug Development, and Nanotechnology Applications

Histopathological growth patterns of liver metastasis: updated consensus guidelines for pattern scoring, perspectives, and recent mechanistic insights

Exploitation of sulfated glycosaminoglycan status for precision medicine of platinums in triple-negative breast cancer

Contact Info

Product

Resources

About