Decellularization of tumours: A new frontier in tissue engineering

Abstract

Cancer is one of the leading causes of death worldwide. The tumour extracellular matrix (ECM) has unique features in terms of composition and mechanical properties, resulting in a structurally and chemically different ECM to that of native, healthy tissues. This paper reviews to date the efforts into decellularization of tumours, which in the authors’ view represents a new frontier in the ever evolving field of tumour tissue engineering. An overview of the ECM and its importance in cancer is given, ending with examples of research using decellularized tumours, which has already indicated potential therapeutic targets, unravelled malignancy mechanisms or response to chemotherapy agents. The review highlights that more research is needed in this area, which can answer important questions related to tumour formation and progression to ultimately identify new and effective therapeutic targets. Within the near-future of personalized medicine, this research can create patient-specific tumour models and therapeutic regimes.

Partial Reconstruction of Uterus Cervix in Rat by Decellularized Human Uterine Cervical Scaffold Combined with Adipose-Derived Stem Cells (ADSCs)

“…Subsequent studies are expected to compare the properties of decellularized ECM including hormone levels, in premenopausal and postmenopausal uterine tissues to optimize the composition of the engineered cervix. In addition, although decellularization can theoretically remove cellular components, ECM is one important constituent of the tumor microenvironment [ 31 , 32 ]. Thus, we do not encourage the selection of postoperative tissue from patients with malignant tumors, to reduce the risk of a new onset cancer.…”

Decellularization of xenografted tumors provides cell-specific in vitro 3D environment

“…This research opens the way to further use of well-characterized xenografted tumor dECM materials as a 3D cell culture platform for basic tumor biology and tumor progression studies, as well as global gene expression studies, drug testing studies, and other in vitro 3D cell culture functional studies relevant in the cancer field. Moreover, it may pave the way to further patient-specific physiologically relevant in vitro 3D research models, in which optimized decellularization may lead to primary tumor cell testing on their own dECM, thereby providing a potentially useful tool for personalized medicine research and diagnosis purposes ( 37 , 49 , 60 – 62 , 64 ).…”

“…Matrices from normal tissue can be used to recognize novel genes inducing cancer or the interactions between cancer cells and healthy ECM. On the other hand, decellularized tumor tissue is more appropriate for studying the influence of pathological ECM on controlling cancer cell function at primary or metastatic sites and the role of ECM as a modulator of cell behavior ( 34 – 37 ).…”

The Matrix Reloaded—The Role of the Extracellular Matrix in Cancer

“…Although the interior of a solid, desmoplastic tumour is subject to compression, the hydrated, gel-forming hyaluronan within the tumour conveys tumour cells with resistance to compressive stress [ 119 ]. Tumour growth can reorganise collagen fibres and change and stretch the fibre orientation toward the tumour circumference [ 120 ]. In a murine model using human head and neck squamous cell carcinoma cells, cellular mechanosignaling induced a progressive linearisation and thickening of collagen that augmented cell growth and survival and created pathways for migratory tumour cells that led to increased metastasis [ 121 ].…”