Cancer-Associated Fibroblasts and their Influence on Tumor Immunity and Immunotherapy

The authors review recent advances in identifying the stroma-dependent mechanisms that regulate cancer-associated inflammation and antitumor immunity, in particular, the interactions between fibroblasts and immune cells.
[eLife]
Barrett, R. L., & Puré, E. (2020). Cancer-associated fibroblasts and their influence on tumor immunity and immunotherapy. ELife, 9, e57243. https://doi.org/10.7554/eLife.57243 Cite
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A Switch in pdgfrb+ Cell-Derived ECM Composition Prevents Inhibitory Scarring and Promotes Axon Regeneration in the Zebrafish Spinal Cord

Scientists demonstrate that a switch in ECM composition is critical for axon regeneration after spinal cord injury and identify the cellular source and components of the growth-promoting lesion ECM.
[Developmental Cell]
Tsata, V., Möllmert, S., Schweitzer, C., Kolb, J., Möckel, C., Böhm, B., Rosso, G., Lange, C., Lesche, M., Hammer, J., Kesavan, G., Beis, D., Guck, J., Brand, M., & Wehner, D. (2021). A switch in pdgfrb+ cell-derived ECM composition prevents inhibitory scarring and promotes axon regeneration in the zebrafish spinal cord. Developmental Cell, 0(0). https://doi.org/10.1016/j.devcel.2020.12.009 Cite
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ILB® Resolves Inflammatory Scarring and Promotes Functional Tissue Repair

Researchers demonstrated that ILB® acts, in part, by downregulating transforming growth factor β signaling genes and by altering gene expression relating to ECM dynamics, leading to tissue remodeling, reduced fibrosis and functional tissue regeneration.
[npj Regenerative Medicine]
Hill, L. J., Botfield, H. F., Begum, G., Qureshi, O., Vigneswara, V., Masood, I., Barnes, N. M., Bruce, L., & Logan, A. (2021). ILB ® resolves inflammatory scarring and promotes functional tissue repair. Npj Regenerative Medicine, 6(1), 1–9. https://doi.org/10.1038/s41536-020-00110-2 Cite
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Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration

The authors provide the first comprehensive overview of how electrospun fiber alignment, diameter, surface nanotopography, surface functionalization, and therapeutic delivery affect Schwann cells in the peripheral nervous system and astrocytes, oligodendrocytes, and microglia in the central nervous system
[Bioengineering]
Puhl, D. L., Funnell, J. L., Nelson, D. W., Gottipati, M. K., & Gilbert, R. J. (2021). Electrospun Fiber Scaffolds for Engineering Glial Cell Behavior to Promote Neural Regeneration. Bioengineering, 8(1), 4. https://doi.org/10.3390/bioengineering8010004 Cite
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Transcriptional Activators YAP/TAZ and AXL Orchestrate Dedifferentiation, Cell Fate, and Metastasis in Human Osteosarcoma

To identify key drivers of metastasis, scientists studied human CCH-OS-D osteocarcinoma cells within a previously described rat acellular lung model that preserved the native lung architecture, extracellular matrix, and capillary network.
[Cancer Gene Therapy]
Lamhamedi-Cherradi, S.-E., Mohiuddin, S., Mishra, D. K., Krishnan, S., Velasco, A. R., Vetter, A. M., Pence, K., McCall, D., Truong, D. D., Cuglievan, B., Menegaz, B. A., Utama, B., Daw, N. C., Molina, E. R., Zielinski, R. J., Livingston, J. A., Gorlick, R., Mikos, A. G., Kim, M. P., & Ludwig, J. A. (2021). Transcriptional activators YAP/TAZ and AXL orchestrate dedifferentiation, cell fate, and metastasis in human osteosarcoma. Cancer Gene Therapy, 1–14. https://doi.org/10.1038/s41417-020-00281-6 Cite
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Hydrogel-Based Colorectal Cancer Organoid Co-Culture Models

The authors report the development of in vitro models consisting of colorectal cancer patient-derived organoid encapsulated within a well-defined three-dimensional hyaluronan-gelatin hydrogel and co-cultured with patient-derived cancer-associated fibroblasts.
[Acta Biomaterialia]
Hydrogel-Based Colorectal Cancer Organoid Co-Culture Models - ScienceDirect. (n.d.). Retrieved January 5, 2021, from https://www.sciencedirect.com/science/article/abs/pii/S1742706120307510?via%3Dihub Cite
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Polarization, Migration and Homotypical Interactions among Prostatic Smooth Muscle Cells in a Laminin 111‐Rich Extracellular Matrix

Researchers tested whether a laminin 111‐rich extracellular matrix could affect smooth muscle cells (SMCs) phenotype and differentiation status. Using time lapse microscopy, image analyses, qRT‐PCR, immunohistochemistry and immunoblotting, and transmission electron microscopy, they showed that SMC acquired a migratory behavior with a decreased expression of differentiation markers and relocation of FAK.
[Cell Biology International]
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Novel Nonsecosteroidal Vitamin D Receptor Modulator Combined with Gemcitabine Enhances Pancreatic Cancer Therapy through Remodeling of the Tumor Microenvironment

Investigators report the design and synthesis of 57 nonsecosteroidal vitamin D receptor (VDR) modulators based on the skeleton of phenyl-pyrrolyl pentane. Among them, compounds C4, I5, and I8 exhibited excellent VDR affinity and effective inhibition of the activation of pancreatic stellate cells (PSCs), as well as potent suppression of the interaction between cancer cells and PSCs in vitro.
[Journal of Medicinal Chemistry]
Kang, Z., Wang, C., Tong, Y., Li, Y., Gao, Y., Hou, S., Hao, M., Han, X., Wang, B., Wang, Q., & Zhang, C. (2020). Novel Nonsecosteroidal Vitamin D Receptor Modulator Combined with Gemcitabine Enhances Pancreatic Cancer Therapy through Remodeling of the Tumor Microenvironment. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.0c01197 Cite
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Extracellular Matrix Composition Modulates the Responsiveness of Differentiated and Stem Pancreatic Cancer Cells to Lipophilic Derivate of Gemcitabine

Researchers analyzed 4-(N)-stearoyl-gemcitabine cytotoxic activity, intracellular uptake, apoptosis, necrosis, and autophagy induction in both Panc1 cell line and their derived cancer stem cells.
[International Journal of MOlecular Sciences]
Forciniti, S., Dalla Pozza, E., Greco, M. R., Amaral Carvalho, T. M., Rolando, B., Ambrosini, G., Carmona-Carmona, C. A., Pacchiana, R., Di Molfetta, D., Donadelli, M., Arpicco, S., Palmieri, M., Reshkin, S. J., Dando, I., & Cardone, R. A. (2021). Extracellular Matrix Composition Modulates the Responsiveness of Differentiated and Stem Pancreatic Cancer Cells to Lipophilic Derivate of Gemcitabine. International Journal of Molecular Sciences, 22(1), 29. https://doi.org/10.3390/ijms22010029 Cite
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Evaluation of Tissue Stem Cell Derived Human Intestinal Organoids, a Physiologically Relevant Model to Evaluate Cytochrome P450 Induction in Gut

Matched human enteroid and colonoid lines, generated from ileal and colon biopsies from two donors, were cultured in extracellular matrix for three days, followed by a single 48h treatment with rifampin, omeprazole, CITCO and phenytoin at concentrations that induce target genes in hepatocytes.
[Drug Metabolism and Disposition]
Evaluation of tissue stem cell derived human intestinal organoids, a physiologically relevant model to evaluate cytochrome P450 induction in gut | Drug Metabolism & Disposition. (n.d.). Retrieved January 5, 2021, from https://dmd.aspetjournals.org/content/early/2020/12/21/dmd.120.000281 Cite
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MaTAR25 lncRNA Regulates the Tensin1 Gene to Impact Breast Cancer Progression

Researchers report on Mammary Tumor Associated RNA 25 (MaTAR25), a nuclear enriched and chromatin associated lncRNA that plays a role in mammary tumor cell proliferation, migration, and invasion, both in vitro and in vivo.
[Nature Communications]
Chang, K.-C., Diermeier, S. D., Yu, A. T., Brine, L. D., Russo, S., Bhatia, S., Alsudani, H., Kostroff, K., Bhuiya, T., Brogi, E., Pappin, D. J., Bennett, C. F., Rigo, F., & Spector, D. L. (2020). MaTAR25 lncRNA regulates the Tensin1 gene to impact breast cancer progression. Nature Communications, 11(1), 6438. https://doi.org/10.1038/s41467-020-20207-y Cite
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