2023-03-17 スイス連邦工科大学チューリッヒ校(ETHZurich)
研究者たちは、これらのチャネルが元々血管だった可能性があることを発見した。これらのチャネルは「腫瘍トラック」と呼ばれ、免疫細胞を捕捉して、がん細胞の増殖を促進することがわかった。健康な組織とは異なり、緩んだ繊維が腫瘍トラックを形成し、これががん細胞が無視される環境を作り出していることが明らかになった。
今後は、腫瘍の発展を制御する微小環境をよりよく理解するための研究が必要だとされている。
ただし、これらは乳がんのマウスでの実験に基づいているため、結果を直接人間に適用できるかどうかはまだ不明である。
<関連情報>
- https://ethz.ch/en/news-and-events/eth-news/news/2023/03/how-tumours-transform-blood-vessels.html
- https://www.sciencedirect.com/science/article/pii/S0945053X23000021
浸潤したCD8+ T細胞とM2マクロファージは、低張力フィブロネクチン線維に富む腫瘍マトリックストラックに保持される。 Infiltrating CD8+ T cells and M2 macrophages are retained in tumor matrix tracks enriched in low tension fibronectin fibers
Charlotte M. Fonta, Thomas Loustau, Chengbei Li, Suchithra Poilil Surendran, Uwe Hansen, Devadarssen Murdamoothoo, Mario C. Benn, Ines Velazquez-Quesada, Raphael Carapito, Gertraud Orend, Viola Vogel
Matrix Biology Available online: 18 January 2023
DOI:https://doi.org/10.1016/j.matbio.2023.01.002
Highlights
- •Tumor associated tracks might originate from endothelial blood vessels.
- •Endothelial-to-mesenchymal transition could be involved in track formation.
- •Use of FnBPA5 tension probe reveals track cores rich in low tension fibronectin fibers.
- •Tenascin-C cellular source impacts track formation and maturation.
- •Retention of CD8+ T cells and M2 macrophages inside the tracks evolves with time and track maturation.
Abstract
Tracks rich in matrix and cells, as described in several cancer types, have immunosuppressive functions and separate tumor nests and stroma, yet their origin is unknown. Immunostainings of cryosections from mouse breast tumors show that these tracks are bordered by an endothelial-like basement membrane, filled with fibers of collagen adjacent to tenascin-C (TNC) and low-tension fibronectin (Fn) fibers. While present in early-stage tumors and maturing with time, tracks still form under TNC KO conditions, however, host (not tumor cell)-derived TNC is important for track maturation. Tumor infiltrating leukocytes (mostly M2 macrophages and CD8+ T cells) are retained in tracks of early-stage tumors. Following track maturation, retained tumor infiltrating leukocyte (TIL) numbers get reduced and more CD8+ TIL enter the tumor nests in the absence of TNC. As these tracks are enriched with platelets and fibrinogen and have a demarcating endothelial-like basement membrane often adjacent to endothelial cells, this suggests a role of blood vessels in the formation of these tracks. The Fn fiber tension probe FnBPA5 colocalizes with TNC and immune cells in the tracks and shows decreased binding in tracks lacking TNC. Consequently, FnBPA5 can serve as probe for tumor matrix tracks that have immune suppressive properties.
