Mimicking the Endometrial Cancer Tumor Microenvironment to Reprogram Tumor-Associated Macrophages in Disintegrable Supramolecular Gelatin Hydrogel

Yujia Huang,1,2,* Qian Feng,3,* Huabo Jiang,1,* Wanding Zhou,1,2 Jinhong Chen,2 Jie Gao,4 Kai Wang,1 Xiaoping Wan,2 Yongsheng Yu1 1Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Huang Y, Feng Q, Jiang H, Zhou W, Chen J, Gao J, Wang K, Wan X, Yu Y
Formato: article
Lenguaje:EN
Publicado: Dove Medical Press 2020
Materias:
Acceso en línea:https://doaj.org/article/2d745892d41642479a7b6698dd78bece
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
id oai:doaj.org-article:2d745892d41642479a7b6698dd78bece
record_format dspace
spelling oai:doaj.org-article:2d745892d41642479a7b6698dd78bece2021-12-02T10:06:28ZMimicking the Endometrial Cancer Tumor Microenvironment to Reprogram Tumor-Associated Macrophages in Disintegrable Supramolecular Gelatin Hydrogel1178-2013https://doaj.org/article/2d745892d41642479a7b6698dd78bece2020-06-01T00:00:00Zhttps://www.dovepress.com/mimicking-the-endometrial-cancer-tumor-microenvironment-to-reprogram-t-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yujia Huang,1,2,* Qian Feng,3,* Huabo Jiang,1,* Wanding Zhou,1,2 Jinhong Chen,2 Jie Gao,4 Kai Wang,1 Xiaoping Wan,2 Yongsheng Yu1 1Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials Science, Fujian Normal University, Fuzhou, People’s Republic of China; 4Institute of Translational Medicine, Shanghai University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoping Wan; Yongsheng Yu Email wanxiaoping61@126.com; yongshengyu@tongji.edu.cnPurpose: Besides the tumor cells themselves, solid tumors are comprised of numerous cell types including infiltrating immune cells such as tumor-associated macrophages (TAMs). TAMs are vital stromal components of host immune system and play a critical role in the development of cancer. TAMs can be divided into two subtypes: M1 tumor-suppressive macrophage and M2 tumor-supportive macrophage. To better address the observations of TAMs functional performance, we describe an in vitro system that mimics the populations of TAMs infiltrated into the tumor mass by using our disintegrable supramolecular gelatin (DSG) hydrogels, which are physically crosslinked by host-guest complexations.Materials and Methods: The host–guest interaction was adopted between the aromatic groups of gelatin and the photocrosslinkable acrylated β-cyclodextrins (Ac-β-CDs) to form the DSG hydrogels. The convenient macrophage/endometrial cancer cells heterospheroid 3D model was set up by DSG hydrogels. RT-PCR and Western blot assays were developed to evaluate the efficiencies of inducers on the macrophages. The ELISA and oxygen saturation assays were performed to measure the secretion of VEGF and consumption of oxygen of tumor and/or macrophages, respectively. To determine the antitumor effects of M2 reprogrammed macrophages in vitro and in vivo, migration assay and tumor xenograft model were used, respectively.Results: The host-guest complexations of DSG hydrogels were controllably broken efficiently by soaking into the solution of competitive guest monomers 1-adamantanamine hydrochloride. The DSG hydrogels help IFN-γ reprogram the M2 to M1 and then decrease the tumor/M2 reprogrammed macrophage cells heterospheroid secretion of VEGF and increase the relative oxygen saturation. Significantly, the co-cultural tumor/M2 reprogrammed group from the disintegrated DSG hydrogels reduced the migration of cancer cells in vitro and the tumor growth in vivo.Conclusion: We obtain a TAMs/tumor microenvironment-responsive 3D model based on the novel DSG hydrogels, and will be of utility in cancer therapy and drug discovery.Keywords: supramolecular hydrogel, disintegration, host-guest complexations, tumor mimic model, tumor-associated macrophages, TAMsHuang YFeng QJiang HZhou WChen JGao JWang KWan XYu YDove Medical Pressarticlesupramolecular hydrogeldisintegrationhost-guest complexationstumor mimic modeltumor-associated macrophages (tams)Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 4625-4637 (2020)
institution DOAJ
collection DOAJ
language EN
topic supramolecular hydrogel
disintegration
host-guest complexations
tumor mimic model
tumor-associated macrophages (tams)
Medicine (General)
R5-920
spellingShingle supramolecular hydrogel
disintegration
host-guest complexations
tumor mimic model
tumor-associated macrophages (tams)
Medicine (General)
R5-920
Huang Y
Feng Q
Jiang H
Zhou W
Chen J
Gao J
Wang K
Wan X
Yu Y
Mimicking the Endometrial Cancer Tumor Microenvironment to Reprogram Tumor-Associated Macrophages in Disintegrable Supramolecular Gelatin Hydrogel
description Yujia Huang,1,2,* Qian Feng,3,* Huabo Jiang,1,* Wanding Zhou,1,2 Jinhong Chen,2 Jie Gao,4 Kai Wang,1 Xiaoping Wan,2 Yongsheng Yu1 1Clinical and Translational Research Center, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, College of Chemistry and Materials Science, Fujian Normal University, Fuzhou, People’s Republic of China; 4Institute of Translational Medicine, Shanghai University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaoping Wan; Yongsheng Yu Email wanxiaoping61@126.com; yongshengyu@tongji.edu.cnPurpose: Besides the tumor cells themselves, solid tumors are comprised of numerous cell types including infiltrating immune cells such as tumor-associated macrophages (TAMs). TAMs are vital stromal components of host immune system and play a critical role in the development of cancer. TAMs can be divided into two subtypes: M1 tumor-suppressive macrophage and M2 tumor-supportive macrophage. To better address the observations of TAMs functional performance, we describe an in vitro system that mimics the populations of TAMs infiltrated into the tumor mass by using our disintegrable supramolecular gelatin (DSG) hydrogels, which are physically crosslinked by host-guest complexations.Materials and Methods: The host–guest interaction was adopted between the aromatic groups of gelatin and the photocrosslinkable acrylated β-cyclodextrins (Ac-β-CDs) to form the DSG hydrogels. The convenient macrophage/endometrial cancer cells heterospheroid 3D model was set up by DSG hydrogels. RT-PCR and Western blot assays were developed to evaluate the efficiencies of inducers on the macrophages. The ELISA and oxygen saturation assays were performed to measure the secretion of VEGF and consumption of oxygen of tumor and/or macrophages, respectively. To determine the antitumor effects of M2 reprogrammed macrophages in vitro and in vivo, migration assay and tumor xenograft model were used, respectively.Results: The host-guest complexations of DSG hydrogels were controllably broken efficiently by soaking into the solution of competitive guest monomers 1-adamantanamine hydrochloride. The DSG hydrogels help IFN-γ reprogram the M2 to M1 and then decrease the tumor/M2 reprogrammed macrophage cells heterospheroid secretion of VEGF and increase the relative oxygen saturation. Significantly, the co-cultural tumor/M2 reprogrammed group from the disintegrated DSG hydrogels reduced the migration of cancer cells in vitro and the tumor growth in vivo.Conclusion: We obtain a TAMs/tumor microenvironment-responsive 3D model based on the novel DSG hydrogels, and will be of utility in cancer therapy and drug discovery.Keywords: supramolecular hydrogel, disintegration, host-guest complexations, tumor mimic model, tumor-associated macrophages, TAMs
format article
author Huang Y
Feng Q
Jiang H
Zhou W
Chen J
Gao J
Wang K
Wan X
Yu Y
author_facet Huang Y
Feng Q
Jiang H
Zhou W
Chen J
Gao J
Wang K
Wan X
Yu Y
author_sort Huang Y
title Mimicking the Endometrial Cancer Tumor Microenvironment to Reprogram Tumor-Associated Macrophages in Disintegrable Supramolecular Gelatin Hydrogel
title_short Mimicking the Endometrial Cancer Tumor Microenvironment to Reprogram Tumor-Associated Macrophages in Disintegrable Supramolecular Gelatin Hydrogel
title_full Mimicking the Endometrial Cancer Tumor Microenvironment to Reprogram Tumor-Associated Macrophages in Disintegrable Supramolecular Gelatin Hydrogel
title_fullStr Mimicking the Endometrial Cancer Tumor Microenvironment to Reprogram Tumor-Associated Macrophages in Disintegrable Supramolecular Gelatin Hydrogel
title_full_unstemmed Mimicking the Endometrial Cancer Tumor Microenvironment to Reprogram Tumor-Associated Macrophages in Disintegrable Supramolecular Gelatin Hydrogel
title_sort mimicking the endometrial cancer tumor microenvironment to reprogram tumor-associated macrophages in disintegrable supramolecular gelatin hydrogel
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/2d745892d41642479a7b6698dd78bece
work_keys_str_mv AT huangy mimickingtheendometrialcancertumormicroenvironmenttoreprogramtumorassociatedmacrophagesindisintegrablesupramoleculargelatinhydrogel
AT fengq mimickingtheendometrialcancertumormicroenvironmenttoreprogramtumorassociatedmacrophagesindisintegrablesupramoleculargelatinhydrogel
AT jiangh mimickingtheendometrialcancertumormicroenvironmenttoreprogramtumorassociatedmacrophagesindisintegrablesupramoleculargelatinhydrogel
AT zhouw mimickingtheendometrialcancertumormicroenvironmenttoreprogramtumorassociatedmacrophagesindisintegrablesupramoleculargelatinhydrogel
AT chenj mimickingtheendometrialcancertumormicroenvironmenttoreprogramtumorassociatedmacrophagesindisintegrablesupramoleculargelatinhydrogel
AT gaoj mimickingtheendometrialcancertumormicroenvironmenttoreprogramtumorassociatedmacrophagesindisintegrablesupramoleculargelatinhydrogel
AT wangk mimickingtheendometrialcancertumormicroenvironmenttoreprogramtumorassociatedmacrophagesindisintegrablesupramoleculargelatinhydrogel
AT wanx mimickingtheendometrialcancertumormicroenvironmenttoreprogramtumorassociatedmacrophagesindisintegrablesupramoleculargelatinhydrogel
AT yuy mimickingtheendometrialcancertumormicroenvironmenttoreprogramtumorassociatedmacrophagesindisintegrablesupramoleculargelatinhydrogel
_version_ 1718397635844374528