دورية أكاديمية
The development of in vitro organotypic 3D vulvar models to study tumor-stroma interaction and drug efficacy.
| العنوان: | The development of in vitro organotypic 3D vulvar models to study tumor-stroma interaction and drug efficacy. |
|---|---|
| المؤلفون: | Wu S; Department of Dermatology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Huisman BW; Center for Human Drug Research, Leiden, 2333 CL, The Netherlands.; Department of Gynecology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Rietveld MH; Department of Dermatology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., Rissmann R; Department of Dermatology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands.; Center for Human Drug Research, Leiden, 2333 CL, The Netherlands.; Leiden Academic Center for Drug Research, Leiden University, Leiden, 2333 CC, The Netherlands., Vermeer MH; Department of Dermatology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., van Poelgeest MIE; Center for Human Drug Research, Leiden, 2333 CL, The Netherlands.; Department of Gynecology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands., El Ghalbzouri A; Department of Dermatology, Leiden University Medical Center, Leiden, 2333 ZA, The Netherlands. a.ghalbzouri@lumc.nl. |
| المصدر: | Cellular oncology (Dordrecht) [Cell Oncol (Dordr)] 2024 Jun; Vol. 47 (3), pp. 883-896. Date of Electronic Publication: 2023 Dec 07. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Springer Country of Publication: Netherlands NLM ID: 101552938 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-3436 (Electronic) Linking ISSN: 22113428 NLM ISO Abbreviation: Cell Oncol (Dordr) Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Dordrecht : Springer |
| مواضيع طبية MeSH: | Vulvar Neoplasms*/pathology , Vulvar Neoplasms*/metabolism , Tumor Microenvironment*/drug effects , Antineoplastic Agents*/pharmacology , Antineoplastic Agents*/therapeutic use, Female ; Humans ; Cell Line, Tumor ; Stromal Cells/pathology ; Stromal Cells/metabolism ; Cancer-Associated Fibroblasts/pathology ; Cancer-Associated Fibroblasts/metabolism ; Fibroblasts/pathology ; Fibroblasts/metabolism ; Fibroblasts/drug effects ; Vulva/pathology ; Models, Biological ; Carcinoma, Squamous Cell/pathology ; Cell Proliferation/drug effects ; Cell Culture Techniques, Three Dimensional/methods ; Epithelial-Mesenchymal Transition/drug effects |
| مستخلص: | Background: Vulvar squamous cell carcinoma (VSCC) is a rare disease with a poor prognosis. To date, there's no proper in vitro modeling system for VSCC to study its pathogenesis or for drug evaluation. Methods: We established healthy vulvar (HV)- and VSCC-like 3D full thickness models (FTMs) to observe the tumor-stroma interaction and their applicability for chemotherapeutic efficacy examination. VSCC-FTMs were developed by seeding VSCC tumor cell lines (A431 and HTB117) onto dermal matrices harboring two NF subtypes namely papillary fibroblasts (PFs) and reticular fibroblasts (RFs), or cancer-associated fibroblasts (CAFs) while HV-FTMs were constructed with primary keratinocytes and fibroblasts isolated from HV tissues. Results: HV-FTMs highly resembled HV tissues in terms of epidermal morphogenesis, basement membrane formation and collagen deposition. When the dermal compartment shifted from PFs to RFs or CAFs in VSCC-FTMs, tumor cells demonstrated more proliferation, EMT induction and stemness. In contrast to PFs, RFs started to lose their phenotype and express robust CAF-markers α-SMA and COL11A1 under tumor cell signaling induction, indicating a favored 'RF-to-CAF' transition in VSCC tumor microenvironment (TME). Additionally, chemotherapeutic treatment with carboplatin and paclitaxel resulted in a significant reduction in tumor-load and invasion in VSCC-FTMs. Conclusion: We successfully developed in vitro 3D vulvar models mimicking both healthy and tumorous conditions which serve as a promising tool for vulvar drug screening programs. Moreover, healthy fibroblasts demonstrate heterogeneity in terms of CAF-activation in VSCC TME which brings insights in the future development of novel CAF-based therapeutic strategies in VSCC. (© 2023. Springer Nature Switzerland AG.) |
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| معلومات مُعتمدة: | 8222-32146 Bontiusstichting |
| فهرسة مساهمة: | Keywords: 3D model; Cancer associated fibroblast; Chemotherapeutics; EMT; Tumor invasion; Vulvar squamous cell carcinoma |
| المشرفين على المادة: | 0 (Antineoplastic Agents) |
| تواريخ الأحداث: | Date Created: 20231206 Date Completed: 20240702 Latest Revision: 20240702 |
| رمز التحديث: | 20240703 |
| DOI: | 10.1007/s13402-023-00902-w |
| PMID: | 38057628 |
| قاعدة البيانات: | MEDLINE |
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