Promoting biological similarity by collagen microfibers in 3D colorectal cancer-stromal tissue: Replicating mechanical properties and cancer stem cell markers
Source abstract
Abstract
The extracellular matrix (ECM) of cancer tissues is rich in dense collagen, contributing to the stiffening of these tissues. Increased stiffness has been reported to promote cancer cell proliferation, invasion, metastasis, and prevent drug delivery. Replicating the structure and mechanical properties of cancer tissue in vitro is essential for developing cancer treatment drugs that target these properties. In this study, we recreated specific characteristics of cancer tissue, such as collagen density and high elastic modulus, using a colorectal cancer cell line as a model. Using our original material, collagen microfibers (CMFs), and a constructed three-dimensional (3D) cancer-stromal tissue model, we successfully reproduced an ECM highly similar to in vivo conditions. Furthermore, our research demonstrated that cancer stem cell markers expressed in the 3D cancer-stromal tissue model more closely mimic in vivo conditions than traditional two-dimensional cell cultures. We also found that CMFs might affect an impact on how cancer cells express these markers. Our 3D CMF-based model holds promise for enhancing our understanding of colorectal cancer and advancing therapeutic approaches. STATEMENT OF SIGNIFICANCE: Reproducing the collagen content and stiffness of cancer tissue is crucial in comprehending the properties of cancer and advancing anticancer drug development. Nonetheless, the use of collagen as a scaffold material has posed challenges due to its poor solubility, hindering the replication of a cancer microenvironment. In this study, we have successfully recreated cancer tissue-specific characteristics such as collagen density, stiffness, and the expression of cancer stem cell markers in three-dimensional (3D) colorectal cancer stromal tissue, utilizing a proprietary material known as collagen microfiber (CMF). CMF proves to be an ideal scaffold material for replicating cancer stromal tissue, and these 3D tissues constructed with CMFs hold promise in contributing to our understanding of cancer and the development of therapeutic drugs.
Source: openalex_inverted_index · Quality: baseline
Research context
OpenAlex topics: Cellular Mechanics and Interactions · Cancer Cells and Metastasis · 3D Printing in Biomedical Research
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (62)
Show source-provided references
1. Gene expression perturbation in vitro - a growing case for three-dimensional (3D) culture systems10.1016/j.semcancer.2005.06.009 ↗
2. Cell interactions with three-dimensional matrices10.1016/S0955-0674(02)00364-2 ↗
3. Capturing complex 3D tissue physiology in vitro10.1038/nrm1858 ↗
4. Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer10.1146/annurev.cellbio.22.010305.104315 ↗
5. 3D cancer models: the need for a complex stroma, compartmentalization and stiffness10.3389/fbioe.2021.660502 ↗
6. Wettability influences cell behavior on superhydrophobic surfaces with different topographies10.1007/s13758-012-0046-6 ↗
7. Response of MG63 osteoblast-like cells onto polycarbonate membrane surfaces with different micropore sizes10.1016/j.biomaterials.2003.11.034 ↗
8. Aligned chitosan-polycaprolactone polyblend nanofibers promote the migration of glioblastoma cells10.1002/adhm.201300092 ↗
9. 3D collagen architecture induces a conserved migratory and transcriptional response linked to vasculogenic mimicry10.1038/s41467-017-01556-7 ↗
10. Macromolecular crowding tunes 3D collagen architecture and cell morphogenesis10.1039/C8BM01188E ↗
11. New collagens, new concepts10.1146/annurev.cb.04.110188.003003 ↗
12. The extracellular matrix at a glance10.1242/jcs.023820 ↗
13. Biomechanical and biomolecular characterization of extracellular matrix structures in human colon carcinomas10.1016/j.matbio.2018.03.016 ↗
14. Sustained growth and three-dimensional organization of primary mammary tumor epithelial cells embedded in collagen gels10.1073/pnas.76.7.3401 ↗
15. Exploring cancer cell behavior in vitro in three-dimensional multicellular bioprintable collagen-based hydrogels
16. 3D in vitro bioengineered tumors based on collagen I hydrogels10.1016/j.biomaterials.2011.07.001 ↗
17. Hydrogel-based colorectal cancer organoid co-culture models10.1016/j.actbio.2020.12.037 ↗
18. Changes in collagen metabolism in prostate cancer: a host response that may alter progression10.1016/S0022-5347(05)65656-X ↗
19. Tensional homeostasis and the malignant phenotype10.1016/j.ccr.2005.08.010 ↗
20. Colorectal cancer stem cells as biomarkers: where it all starts?10.1002/jso.23330 ↗
21. Concise review: colorectal cancer stem cells10.1002/stem.1031 ↗
22. Type I collagen inhibits differentiation and promotes a stem cell-like phenotype in human colorectal carcinoma cells10.1038/sj.bjc.6605143 ↗
23. Matrix stiffness and colorectal cancer10.2147/OTT.S231010 ↗
24. 3D collagen microfibers stimulate the functionality of preadipocytes and maintain the phenotype of mature adipocytes for long term cultures10.1016/j.actbio.2018.11.048 ↗
25. Collagen microfibers induce blood capillary orientation and open vascular lumen
26. Wholly Vascularized Millimeter-Sized Engineered Tissues by Cell-Sized Microscaffolds
27. Dynamic analysis of Porphyromonas gingivalis invasion into blood capillaries during the infection process in host tissues using a vascularized three-dimensional human gingival model10.1039/D1BM00831E ↗
28. The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets10.1038/ncomms8002 ↗
29. The Hippo pathway effectors YAP and TAZ promote cell growth by modulating amino acid signaling to mTORC110.1038/cr.2015.140 ↗
30. iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data10.1186/s12859-018-2486-6 ↗
31. A red-shifted fluorescent substrate for aldehyde dehydrogenase10.1038/ncomms4662 ↗
32. YAP/TAZ as master regulators in cancer: modulation, function and therapeutic approaches
33. Ki-67: more than a proliferation marker10.1007/s00412-018-0659-8 ↗
34. U. Gnthert, M. Hofmann, W. Rudy, S. Reber, M. Zer, I. Hsusmann, S. Mstzku, A. Wenzel, A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells, 65 (1991) 13–24. https://doi.org/10.1016/0092-8674(91)90403-L.10.1016/0092-8674(91)90403-L ↗
35. Cell-matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca2+ influx and PKC activation10.1083/jcb.200310024 ↗
36. Mechanism and biological significance of CD44 cleavage10.1111/j.1349-7006.2004.tb03179.x ↗
37. Concise review: emerging role of CD44 in cancer stem cells: a promising biomarker and therapeutic target10.5966/sctm.2015-0048 ↗
38. Clinical significance of CD44 variant 9 expression as a prognostic indicator in bladder cancer10.3892/or.2016.5061 ↗
39. Expression of a CD44 variant containing exons 8 to 10 is a useful independent factor for the prediction of prognosis in colorectal cancer patients10.1200/JCO.1996.14.4.1122 ↗
40. CD44variant exon 9 plays an important role in colon cancer initiating cells10.18632/oncotarget.1048 ↗
41. Reduction of liver metastasis stiffness improves response to bevacizumab in metastatic colorectal cancer10.1016/j.ccell.2020.05.005 ↗
42. Matrix stiffness corresponding to strictured bowel induces a fibrogenic response in human colonic fibroblasts10.1097/MIB.0b013e3182813297 ↗
43. YAP/TAZ at the roots of cancer10.1016/j.ccell.2016.05.005 ↗
44. A time for YAP1: tumorigenesis, immunosuppression and targeted therapy10.1002/ijc.31561 ↗
45. The roles of the Hippo pathway in cancer metastasis10.1016/j.cellsig.2016.08.004 ↗
46. YAP/TAZ activation as a target for treating metastatic cancer10.3390/cancers10040115 ↗
47. YAP/TAZ signaling as a molecular link between fibrosis and cancer10.3390/ijms19113674 ↗
48. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth10.1038/ncb3216 ↗
49. β-Catenin-driven cancers require a YAP1 transcriptional complex for survival and tumorigenesis10.1016/j.cell.2012.11.026 ↗
50. Role of YAP/TAZ in cell-matrix adhesion-mediated signalling and mechanotransduction10.1016/j.yexcr.2015.10.034 ↗
51. Regulation of small GTPases by GEFs, GAPs, and GDIs10.1152/physrev.00003.2012 ↗
52. Erratum: genomic analysis of metastasis reveals an essential role for RhoC (Nature (2000) 406 (532-535))10.1038/35082119 ↗
53. Molecular mechanisms of colon cancer progression and metastasis: recent insights and advancements
54. Cell response to mechanical microenvironment cues via Rho signaling: from mechanobiology to mechanomedicine10.1016/j.actbio.2023.01.039 ↗
55. Optimum 3D matrix stiffness for maintenance of cancer stem cells is dependent on tissue origin of cancer cells10.1371/journal.pone.0132377 ↗
56. CD44: a multifunctional cell surface adhesion receptor is a regulator of progression and metastasis of cancer cells10.3389/fcell.2017.00018 ↗
57. CD44v9 induces stem cell-like phenotypes in human cholangiocarcinoma10.3389/fcell.2020.00417 ↗
58. Organoid cultures for the analysis of cancer phenotypes10.1016/j.gde.2013.11.012 ↗
59. E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers10.1002/j.1460-2075.1995.tb00301.x ↗
60. Axis of evil: molecular mechanisms of cancer metastasis10.1038/sj.onc.1206757 ↗
61. E-cadherin is required for metastasis in multiple models of breast cancer10.1038/s41586-019-1526-3 ↗
62. E-cadherin regulates proliferation of colorectal cancer stem cells through NANOG