Three-Dimensional Culture System of Cancer Cells Combined with Biomaterials for Drug Screening
TL;DR: 3D culture systems of cancer cells combined with several biomaterials for anticancer drug screening are introduced and a brief summary of the cancer environment is introduced.
Abstract: Anticancer drug screening is one of the most important research and development processes to develop new drugs for cancer treatment. However, there is a problem resulting in gaps between the in vitro drug screening and preclinical or clinical study. This is mainly because the condition of cancer cell culture is quite different from that in vivo. As a trial to mimic the in vivo cancer environment, there has been some research on a three-dimensional (3D) culture system by making use of biomaterials. The 3D culture technologies enable us to give cancer cells an in vitro environment close to the in vivo condition. Cancer cells modified to replicate the in vivo cancer environment will promote the biological research or drug discovery of cancers. This review introduces the in vitro research of 3D cell culture systems with biomaterials in addition to a brief summary of the cancer environment.
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TL;DR: In this article, a review of recent regenerative medicine based on biomaterial technologies is presented, where the authors highlight the importance of cell activity enhancement in the body for drug research because the difference in cell condition between in vitro and in vivo leads to a gap in drug evaluation.
Abstract: This review aims to show case recent regenerative medicine based on biomaterial technologies. Regenerative medicine has arousing substantial interest throughout the world, with “The enhancement of cell activity” one of the essential concepts for the development of regenerative medicine. For example, drug research on drug screening is an important field of regenerative medicine, with the purpose of efficient evaluation of drug effects. It is crucial to enhance cell activity in the body for drug research because the difference in cell condition between in vitro and in vivo leads to a gap in drug evaluation. Biomaterial technology is essential for the further development of regenerative medicine because biomaterials effectively support cell culture or cell transplantation with high cell viability or activity. For example, biomaterial-based cell culture and drug screening could obtain information similar to preclinical or clinical studies. In the case of in vivo studies, biomaterials can assist cell activity, such as natural healing potential, leading to efficient tissue repair of damaged tissue. Therefore, regenerative medicine combined with biomaterials has been noted. For the research of biomaterial-based regenerative medicine, the research objective of regenerative medicine should link to the properties of the biomaterial used in the study. This review introduces regenerative medicine with biomaterial.
37 citations
TL;DR: This review summarizes the current evidence on the role of TAMs in HCC pathogenesis and progression, as well as in their potential involvement in tumor therapy, shedding light on emerging anticancer treatment methods targeting monocytes.
Abstract: Simple Summary Hepatocellular carcinoma (HCC) constitutes a major health burden, accounting for >80% of primary liver cancers globally. Inflammation has come into the spotlight as a hallmark of cancer, and it is evident that tumor-associated inflammation drives the involvement of monocytes in tumor growth and metastasis. Tumor-associated macrophages (TAMs) actively participate in tumor-related inflammation, representing the main type of inflammatory cells in the tumor microenvironment, setting the crosstalk between tumor and stromal cells. Infiltrating TAMs exert either anti-tumorigenic (M1) or pro-tumorigenic (M2) functions. In most solid human tumors, increased TAM infiltration has been associated with enhanced tumor growth and metastasis, while other studies showcase that under certain conditions, TAMs exhibit cytotoxic and tumoricidal activity, inhibiting the progression of cancer. In this review, we summarize the current evidence on the role of macrophages in the pathogenesis and progression of HCC and we highlight their potential utilization in HCC prognosis and therapy. Abstract Hepatocellular carcinoma (HCC) constitutes a major health burden globally, and it is caused by intrinsic genetic mutations acting in concert with a multitude of epigenetic and extrinsic risk factors. Cancer induces myelopoiesis in the bone marrow, as well as the mobilization of hematopoietic stem and progenitor cells, which reside in the spleen. Monocytes produced in the bone marrow and the spleen further infiltrate tumors, where they differentiate into tumor-associated macrophages (TAMs). The relationship between chronic inflammation and hepatocarcinogenesis has been thoroughly investigated over the past decade; however, several aspects of the role of TAMs in HCC development are yet to be determined. In response to certain stimuli and signaling, monocytes differentiate into macrophages with antitumor properties, which are classified as M1-like. On the other hand, under different stimuli and signaling, the polarization of macrophages shifts towards an M2-like phenotype with a tumor promoting capacity. M2-like macrophages drive tumor growth both directly and indirectly, via the suppression of cytotoxic cell populations, including CD8+ T cells and NK cells. The tumor microenvironment affects the response to immunotherapies. Therefore, an enhanced understanding of its immunobiology is essential for the development of next-generation immunotherapies. The utilization of various monocyte-centered anticancer treatment modalities has been under clinical investigation, selectively targeting and modulating the processes of monocyte recruitment, activation and migration. This review summarizes the current evidence on the role of TAMs in HCC pathogenesis and progression, as well as in their potential involvement in tumor therapy, shedding light on emerging anticancer treatment methods targeting monocytes.
34 citations
TL;DR: The extracellular matrix (ECM) has pleiotropic effects, ranging from cell adhesion to cell survival, and the use of ECM and ECM-like scaffolds has separated the field into two distinct areas.
Abstract: The extracellular matrix (ECM) has pleiotropic effects, ranging from cell adhesion to cell survival. In tissue engineering, the use of ECM and ECM-like scaffolds has separated the field into two distinct areas—scaffold-based and scaffold-free. Scaffold-free techniques are used in creating reproducible cell aggregates which have massive potential for high-throughput, reproducible drug screening and disease modeling. Though, the lack of ECM prevents certain cells from surviving and proliferating. Thus, tissue engineers use scaffolds to mimic the native ECM and produce organotypic models which show more reliability in disease modeling. However, scaffold-based techniques come at a trade-off of reproducibility and throughput. To bridge the tissue engineering dichotomy, we posit that finding novel ways to incorporate the ECM in scaffold-free cultures can synergize these two disparate techniques.
33 citations
TL;DR: The role of inflammation during the development and progression of HCC is described by focusing on TME by describing the most recent therapeutic advances for HCC and possible combinatorial treatment options.
Abstract: The prevalence of liver cancer is constantly rising, with increasing incidence and mortality in Europe and the USA in recent decades. Among the different subtypes of liver cancers, hepatocellular carcinoma (HCC) is the most commonly diagnosed liver cancer. Besides advances in diagnosis and promising results of pre-clinical studies, HCC remains a highly lethal disease. In many cases, HCC is an effect of chronic liver inflammation, which leads to the formation of a complex tumor microenvironment (TME) composed of immune and stromal cells. The TME of HCC patients is a challenge for therapies, as it is involved in metastasis and the development of resistance. However, given that the TME is an intricate system of immune and stromal cells interacting with cancer cells, new immune-based therapies are being developed to target the TME of HCC. Therefore, understanding the complexity of the TME in HCC will provide new possibilities to design novel and more effective immunotherapeutics and combinatorial therapies to overcome resistance to treatment. In this review, we describe the role of inflammation during the development and progression of HCC by focusing on TME. We also describe the most recent therapeutic advances for HCC and possible combinatorial treatment options.
29 citations
TL;DR: This review discusses the complex interactions between CAFs and the various populations of normal and neoplastic cells that interact within the dynamic confines of the tumor microenvironment with a focus on the involved pathways and genes.
Abstract: Simple Summary The tumor microenvironment plays an important role in determining the biological behavior of several of the more aggressive malignancies. Among the various cell types evident in the tumor “field”, cancer-associated fibroblasts (CAFs) are a heterogenous collection of activated fibroblasts secreting a wide repertoire of factors that regulate tumor development and progression, inflammation, drug resistance, metastasis and recurrence. Insensitivity to chemotherapeutics and metastatic spread are the major contributors to cancer patient mortality. This review discusses the complex interactions between CAFs and the various populations of normal and neoplastic cells that interact within the dynamic confines of the tumor microenvironment with a focus on the involved pathways and genes. Abstract Cancer-associated fibroblasts (CAFs) are a heterogenous population of stromal cells found in solid malignancies that coexist with the growing tumor mass and other immune/nonimmune cellular elements. In certain neoplasms (e.g., desmoplastic tumors), CAFs are the prominent mesenchymal cell type in the tumor microenvironment, where their presence and abundance signal a poor prognosis in multiple cancers. CAFs play a major role in the progression of various malignancies by remodeling the supporting stromal matrix into a dense, fibrotic structure while secreting factors that lead to the acquisition of cancer stem-like characteristics and promoting tumor cell survival, reduced sensitivity to chemotherapeutics, aggressive growth and metastasis. Tumors with high stromal fibrotic signatures are more likely to be associated with drug resistance and eventual relapse. Clarifying the molecular basis for such multidirectional crosstalk among the various normal and neoplastic cell types present in the tumor microenvironment may yield novel targets and new opportunities for therapeutic intervention. This review highlights the most recent concepts regarding the complexity of CAF biology including CAF heterogeneity, functionality in drug resistance, contribution to a progressively fibrotic tumor stroma, the involved signaling pathways and the participating genes.
29 citations
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TL;DR: The evidence in favour of alternative macrophage activation by the TH2-type cytokines interleukin-4 (IL-4) and IL-13 is assessed, and its limits and relevance to a range of immune and inflammatory conditions are defined.
Abstract: The classical pathway of interferon-gamma-dependent activation of macrophages by T helper 1 (T(H)1)-type responses is a well-established feature of cellular immunity to infection with intracellular pathogens, such as Mycobacterium tuberculosis and HIV. The concept of an alternative pathway of macrophage activation by the T(H)2-type cytokines interleukin-4 (IL-4) and IL-13 has gained credence in the past decade, to account for a distinctive macrophage phenotype that is consistent with a different role in humoral immunity and repair. In this review, I assess the evidence in favour of alternative macrophage activation in the light of macrophage heterogeneity, and define its limits and relevance to a range of immune and inflammatory conditions.
5,930 citations
TL;DR: Recent studies have shown that monocyte heterogeneity is conserved in humans and mice, allowing dissection of its functional relevance: the different monocyte subsets seem to reflect developmental stages with distinct physiological roles, such as recruitment to inflammatory lesions or entry to normal tissues.
Abstract: Heterogeneity of the macrophage lineage has long been recognized and, in part, is a result of the specialization of tissue macrophages in particular microenvironments. Circulating monocytes give rise to mature macrophages and are also heterogeneous themselves, although the physiological relevance of this is not completely understood. However, as we discuss here, recent studies have shown that monocyte heterogeneity is conserved in humans and mice, allowing dissection of its functional relevance: the different monocyte subsets seem to reflect developmental stages with distinct physiological roles, such as recruitment to inflammatory lesions or entry to normal tissues. These advances in our understanding have implications for the development of therapeutic strategies that are targeted to modify particular subpopulations of monocytes.
4,861 citations
"Three-Dimensional Culture System of..." refers background in this paper
...M1 macrophages (proinflammatory) have a capacity of inflammation induction, chronic inflammation, and pathogen defense [36,37]....
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TL;DR: These functionally polarized cells, and similarly oriented or immature dendritic cells present in tumors, have a key role in subversion of adaptive immunity and in inflammatory circuits that promote tumor growth and progression.
4,728 citations
"Three-Dimensional Culture System of..." refers background in this paper
...TAM are generally recognized as M2-type macrophages [40,41]....
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TL;DR: In addition to their role in extracellular matrix turnover and cancer cell migration, MMPs regulate signaling pathways that control cell growth, inflammation, or angiogenesis and may even work in a nonproteolytic manner.
4,185 citations
TL;DR: Using a coimplantation tumor xenograft model, it is demonstrated that carcinoma-associated fibroblasts extracted from human breast carcinomas promote the growth of admixed breast carcinoma cells significantly more than do normal mammaries derived from the same patients.
3,373 citations
"Three-Dimensional Culture System of..." refers background in this paper
...This proliferation enhancement was induced by stromal cell-derived factor-1 (SDF-1) secreted [29]....
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