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2022．02
細胞動滋動：淺談膠原蛋白 (Collagen)與細胞移動
在體外培養中使用的細胞外基質（Extracellular matrix, ECM）蛋白，如膠原蛋白 (collagen)和彈性蛋白 (Elastin)，許多文獻指出其在許多情況下可以優化細胞的狀態與行為；而細胞外基質中最豐富的：collagen被驗證可用於維持大多數間質組織和器官結構，且膠原蛋白同時對細胞而言是為引發多種細胞功能的機制信號，其訊號通過細胞膜上的多種受體，如：integrins, discoidin domain receptors DDR1與 2, OSCAR, GPVI, G6b-B, LAIR-1 of the leukocyte receptor complex (LRC) 以及甘露糖家族受體(mannose family receptor)。2 自1956年以來，膠原蛋白不斷地被證實可改變細胞的形態、協助細胞遷移和黏附，甚至影響細胞分化。3
collagen和integrins引發的細胞移動對幾種細胞類型至關重要。1
四種不同的integrin（α1β1、α2β1、α10β1和α11β1）已被證實與collagen結合以促進細胞移動。α1和α2鏈的表達在血管內皮生長因數分泌時增加，對體內的淋巴管生成是必需的。α11β1整合素在間充質組織的一個亞群中表達，並調節PDGF依賴的膠原基質上的趨化作用。
此外，uPARAP/Endo180被證實協助纖維母細胞 (fibroblasts)與collagen的最初粘附，並加速這些細胞在纖維狀膠原基質上的遷移 8, 9, 10, 11 。另在骨骼中，uPARAP/Endo180高度表達於發育過程中的軟骨內和膜內骨化部位的成骨細胞和骨細胞。8
研究不斷地探討與證實collagen對細胞至關重要，因為它與多種受體結合、進而誘發各種細胞生理機制。TOOLS推出了業界最高標準的collagen產品，所有TOOLS Collagen I產品的品質皆>95% 純度(SDS-PAGE驗證)和超低內毒素水準（通過LAL檢測≤1.0 EU/ml）。TOOLS Collagen I系列產品包含凍乾形式和3-4mg/mL的溶液形式，滿足各種應用與操作更為彈性。TOOLS Collagen I產品經實驗證實模擬細胞外環境，促進細胞的粘附、生長、分化和遷移，是建立3D和2.5D細胞培養模式的最理想選擇。
查看更多關於TOOLS膠原蛋白產品和基於支架的 3D培養套件的細節
Reference
1. Hood JD, Cheresh DA. Role of integrins in cell invasion and migration. Nat Rev Cancer. 2002 Feb;2(2):91-100.
2. Boraschi-Diaz I, Wang J, Mort JS and Komarova SV (2017) Collagen Type I as a Ligand for Receptor-Mediated Signaling. Front. Phys. 5:12.
3. Erhmann and Gey in 1956 (48) were the first to systematically compare growth of many cell strains and tissue explants on collagen substrates with growth on glass. They reported that collagen gels in many cases improved cell growth. Subsequently, it has been observed that collagen substrates alter the morphology (43, 235), migration (181), and adhesion (97, 113, 159) of cells and, in some cases, differentiation (124, 184).
4. Hong YK, Lange-Asschenfeldt B, Velasco P. et al. VEGF-A promotes tissue repair- associated lymphatic vessel formation via VEGFR-2 and the alpha1beta1 and alpha2beta1 integrins. FASEB J. 2004;18(10):1111–1113.
5. Bengtsson T, Aszodi A, Nicolae C. et al. Loss of alpha10beta1 integrin expression leads to moderate dysfunction of growth plate chondrocytes. J Cell Sci. 2005;118(Pt 5):929–936
6. Popova SN, Rodriguez-Sanchez B, Liden A. et al. The mesenchymal alpha11beta1 integrin attenuates PDGF-BB-stimulated chemotaxis of embryonic fibroblasts on collagens. Dev Biol. 2004;270(2):427–442.
7. Tiger CF, Fougerousse F, Grundstrom G. et al. alpha11beta1 integrin is a receptor for interstitial collagens involved in cell migration and collagen reorganization on mesenchymal nonmuscle cells. Dev Biol. 2001;237(1):116–129.
8. Engelholm LH, List K, Netzel-Arnett S, Cukierman E, Mitola DJ, Aaronson H, et al. uPARAP/Endo180 is essential for cellular uptake of collagen and promotes fibroblast collagen adhesion. J Cell Biol. (2003) 160:1009–15.
9. Jürgensen HJ, Madsen DH, Ingvarsen S, Melander MC, Gårdsvoll H, Patthy L, et al. A novel functional role of collagen glycosylation: interaction with the endocytic collagen receptor uparap/ENDO180. J Biol Chem. (2011) 286:32736–48.
10. Madsen DH, Engelholm LH, Ingvarsen S, Hillig T, Wagenaar-Miller RA, Kjøller L, et al. Extracellular collagenases and the endocytic receptor, urokinase plasminogen activator receptor-associated protein/Endo180, cooperate infibroblast-mediated collagen degradation. J. Biol Chem. (2007) 282:27037–45.
11. Engelholm LH, Melander MC, Hald A, Persson M, Madsen DH, Jürgensen HJ, et al. Targeting a novel bone degradation pathway in primary bone cancer by inactivation of the collagen receptor uPARAP/Endo180. J Pathol. (2016) 238:120–33.
