The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

Senthebane, Dimakatso Alice; Jonker, Tina; Rowe, Arielle; Thomford, Nicholas Ekow; Munro, Daniella; Dandara, Collet; Wonkam, Ambroise; Govender, Dhirendra; Calder, Bridget; Soares, Nelson C.; Blackburn, Jonathan M.; Parker, M. Iqbal; Dzobo, Kevin

doi:10.3390/ijms19102861

Cited by 107 publications

(172 citation statements)

References 222 publications

(271 reference statements)

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“…As reported by Senthebane and colleagues, CAFs and other TM components can also display anti-tumorigenic effects especially during the early stages of tumor development [18]. Our data revealed that normal fibroblast-derived ECM limits cancer cell proliferation and migration compared to an ECM from fibroblasts co-cultured with cancer cells [17]. Further evidence of the involvement of CAFs or their normal counterparts in anti-tumorigenic behaviour comes from studies of breast cancer.…”

Section: Cancer-associated Fibroblasts and Other Stromal Cells Interasupporting

confidence: 74%

“…CAFs are known to release several other angiogenic factors such as PDGF-C, VEGF-A, and secreted frizzled-related protein-2 (SFRP2) [41]. Through the synthesis of ECM proteins and generation of ECM stiffness, CAFs also influence blood vessel formation and also the flow of blood through the tumor [17,202].…”

Section: Cancer-associated Fibroblasts and Carcinogenesismentioning

confidence: 99%

“…including our recent publication have demonstrated that MSCs can be transformed into CAFs [18,76,132,291,292]. Senthebane and colleagues demonstrated the influence of the ECM in tumor growth and chemoresistance [17]. Importantly, the presence of ECM proteins including type I collagen and fibronectin was shown to affect drug delivery to cancer cells, with the knockdown of both ECM proteins showing increased drug-induced cancer cell death [17].…”

Section: Caf-directed Therapiesmentioning

confidence: 99%

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Cancer-associated Fibroblasts: Origins, Heterogeneity and Functions in Tumor Microenvironment

Dzobo¹

2020

Preprint

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Current therapeutic strategies targeting cancer cells within solid tumors have displayed limited success owing to the presence of non-cancer components referred to as the tumor stroma within the tumor microenvironment (TM). These stromal cells, extracellular matrix and blood vessels influence cancer cell response to therapy and play key roles in tumor relapse and resistance. Of the stromal cells present in the TM, a lot of attention has been given to cancer-associated fibroblasts (CAFs) as they are the most abundant and are important in cancer initiation, progression and therapy resistance. In this updated review I emphasize the role of CAFs in the regulation of tumor cell behaviour and reveal how CAF-derived factors and signaling influence tumor cell heterogeneity and development of novel strategies to combat cancer. To investigate the expression of CAF markers in tumor tissues versus normal tissues, transcriptomic data from The Cancer Genome Atlas (TCGA) and the Gene Expression Profiling Interactive Analysis (GEPIA) databases was used. Bioinformatic analysis reveals differential expression of CAF markers in several cancer types, underscoring the need for further multiomics and biochemical studies on CAFs, CAF subsets and markers. Differences in CAF markers’ expression could be due to different cellular origins as well as the effect of cancer-specific tumor microenvironmental effect on CAFs. Lastly, I present recent advances in therapeutic targeting of CAFs and the success of such endeavours or its lack thereof. It is recommended that for patients’ outcomes to improve, cancer treatment be combinatorial in nature, targeting both cancer cells and stromal cells and interactions.

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Section: Cancer-associated Fibroblasts and Other Stromal Cells Interasupporting

confidence: 74%

Section: Cancer-associated Fibroblasts and Carcinogenesismentioning

confidence: 99%

Section: Caf-directed Therapiesmentioning

confidence: 99%

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Cancer-associated Fibroblasts: Origins, Heterogeneity and Functions in Tumor Microenvironment

Dzobo¹

2020

Preprint

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“…Compared to the 2D culture, the extracellular matrix (ECM)related proteins collagen type I alpha 1 (COL1A1), fibronectin 1 (FN1) and cell connection-related proteins E-cadherin, N-cadherin, gap junction alpha-1 protein (GJA1) were enhanced in soft sarcoma cells of 3D culture (Bai et al, 2015). Another research also showed that the ECM-related proteins COL1A1 and FN were enhanced in oesophageal cancer cells cultured in 3D culture (Senthebane et al, 2018). Meanwhile, the 3D culture could bridge the gap between extremely simplified 2D cell culture and complex animal models (Zanoni et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

A new three‐dimensional glass scaffold increases the in vitro maturation efficiency of buffalo (Bubalus bubalis) oocyte via remodelling the extracellular matrix and cell connection of cumulus cells

Shen

Wang

et al. 2020

Reprod Domestic Animals

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At present, many three‐dimensional (3D) culture systems have been reported, improving the oocyte quality of in vitro maturation (IVM), yet the mechanism still needs to be further explored. Here we examined the effects of a new self‐made 3D glass scaffold on buffalo oocyte maturation; meanwhile, the underlying mechanism on buffalo oocyte maturation was also detected. Compared to the two‐dimensional (2D) glass dish culture, results revealed that the 3D culture can improve the first polar body rate of oocytes, subsequent cleavage and blastocysts rate of parthenogenetic activation embryos (p < .05). The extracellular matrix‐related proteins COL1A1, COL2A1, COL3A1, FN and cell connection‐related proteins N‐cadherin, E‐cadherin, GJA1 were found higher in cumulus cells of 3D culture. Moreover, in cumulus cells, proteins of the PI3K/AKT pathway reported being regulated by FN and E‐cadherin including PI3K P85 and p‐AKT were also higher in 3D culture. Furthermore, proapoptosis proteins P53, BAX, caspase‐3 were lower in both cumulus cells and oocytes in 3D culture, while proteins PCNA and BCL2 showed the opposite result. Results also showed that the apoptosis was inhibited, and the proliferation was enhanced in cumulus cells of 3D culture. Finally, the cumulus expansion‐related genes HAS2, CD44, HMMR, PTX3, PTGS2 were found higher in cumulus cells of 3D culture. Taken together, the 3D culture could promote oocyte maturation by regulating proteins correlated with the ECM, cell connection and PI3K/AKT pathway, inhibiting the apoptosis of cumulus cells and oocytes, enhancing the proliferation of cumulus cells and the cumulus expansion.

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“…The same study revealed that growth factors differ between different tissues and certain ECM proteins are more abundant in certain tissues. Similar studies have been performed using cell-derived ECMs and shown that ECM proteins are essential for cancer cell migration and survival [116]. Thus, it is important to choose the right organ during dECM bioink manufacturing.…”

Section: Decm Bioinks Modificationsmentioning

confidence: 69%

Trends in Decellularized Extracellular Matrix Bioinks for 3D Printing: Inspiring a new Kind of Medicine

Dzobo¹,

Motaung²,

Adesida³

2019

Preprint

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The promise of regenerative medicine and tissue engineering is founded on the ability to regenerate diseased or damaged tissues and organs into functional tissues and organs or the creation of new tissues and organs altogether. In theory, all damaged and diseased tissues and organs can be regenerated or created using different configurations and combinations of extracellular matrix, cells and inductive biomolecules. Currently, regenerative medicine and tissue engineering can allow the improvement of patients’ quality of life through availing novel treatment options. Tissues and organs have a specific ECM, with specific proteins and factors released by cells residing within the local microenvironment. The coupling of regenerative medicine and tissue engineering field with 3D printing is revolutionizing the treatment of patients in a huge way. 3D bioprinting allows the proper placement of cells and ECMs, allowing the recapitulation of native microenvironments of tissues and organs. 3D bioprinting utilizes different bioinks made up of different formulations of ECM/biomaterials, biomolecules and even cells. The choice of the bioink used during 3D bioprinting is very important as properties such as printability, compatibility and physical strength influence the final construct printed. The extracellular matrix (ECM) provides both physical and mechanical microenvironment needed by cells to survive and proliferate. Decellularized ECM bioink contains biochemical cues from the original native ECM and also the right proportions of ECM proteins. Different techniques and characterization methods are used to derive bioinks from several tissues and organs and to evaluate their quality. This review discusses the uses of decellularized ECM bioinks and argues that they represent the most biomimetic bioinks available. In addition, we briefly discuss some polymer-based bioinks utilized in 3D bioprinting.

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The Role of Tumor Microenvironment in Chemoresistance: 3D Extracellular Matrices as Accomplices

Cited by 107 publications

References 222 publications

Cancer-associated Fibroblasts: Origins, Heterogeneity and Functions in Tumor Microenvironment

Cancer-associated Fibroblasts: Origins, Heterogeneity and Functions in Tumor Microenvironment

A new three‐dimensional glass scaffold increases the in vitro maturation efficiency of buffalo (Bubalus bubalis) oocyte via remodelling the extracellular matrix and cell connection of cumulus cells

Trends in Decellularized Extracellular Matrix Bioinks for 3D Printing: Inspiring a new Kind of Medicine

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