内容紹介
Effect of Natural Killer Cell Infiltration on the Growth of Breast Cancer Patient-Derived Tumor Xenografts
Summary
Natural killer(NK)cells, a component of the innate immunity, play important roles in tumor suppression. In this study, three human breast cancer patient-derived tumor xenografts(PDXs), established by the transplantation of surgical specimens, were passaged in immunodeficient NOD/SCID mice or NSG mice, that further lacks NK cell activity. The intensity of the relative growth suppression between NOD/SCID and NSG mice was clearly different depending on the PDX lines, and it was associated with the intensities of the CD49b-positive NK cell infiltration in the PDX tumor tissues. However, no obvious association was observed between the mRNA expression levels of the NK cell ligands in the PDX tumor cells and the intensity of NK cell infiltration into the PDX tumors. These results suggest that the suppressive effect of NK cells on the growth of breast cancer PDX is highly variable depending on the PDX lines. Further studies are needed to elucidate the molecular mechanism of NK cell infiltration in PDX tumors.
要旨
NK細胞は自然免疫の主因子の一つであり,悪性腫瘍の増殖抑制にも重要な役割をもつ。本研究では,ヒト乳がん手術検体を直接移植して樹立した3種類のヒトがん異種移植腫瘍(patient-derived tumor xenograft: PDX)を,高度免疫不全マウスであるNOD/SCIDマウスと,さらにNK細胞の活性を欠くNSGマウスに継代移植した。NSGマウスと比較したNOD/SCIDマウスでの腫瘍増殖抑制の程度はPDXの系統により大きく異なり,抗CD49b抗体で標識されるNK細胞の浸潤の程度と関連した。しかし,各種のNK細胞リガンドのPDX腫瘍細胞における発現と,NK細胞の浸潤度には関連を認めなかった。以上より,NK細胞による増殖抑制の程度は,乳がんPDX腫瘍により大きく異なることが示唆された。乳がんPDX組織へのNK細胞浸潤にかかわる分子機構については,さらなる検討が必要である。
目次
Summary
Natural killer(NK)cells, a component of the innate immunity, play important roles in tumor suppression. In this study, three human breast cancer patient-derived tumor xenografts(PDXs), established by the transplantation of surgical specimens, were passaged in immunodeficient NOD/SCID mice or NSG mice, that further lacks NK cell activity. The intensity of the relative growth suppression between NOD/SCID and NSG mice was clearly different depending on the PDX lines, and it was associated with the intensities of the CD49b-positive NK cell infiltration in the PDX tumor tissues. However, no obvious association was observed between the mRNA expression levels of the NK cell ligands in the PDX tumor cells and the intensity of NK cell infiltration into the PDX tumors. These results suggest that the suppressive effect of NK cells on the growth of breast cancer PDX is highly variable depending on the PDX lines. Further studies are needed to elucidate the molecular mechanism of NK cell infiltration in PDX tumors.
要旨
NK細胞は自然免疫の主因子の一つであり,悪性腫瘍の増殖抑制にも重要な役割をもつ。本研究では,ヒト乳がん手術検体を直接移植して樹立した3種類のヒトがん異種移植腫瘍(patient-derived tumor xenograft: PDX)を,高度免疫不全マウスであるNOD/SCIDマウスと,さらにNK細胞の活性を欠くNSGマウスに継代移植した。NSGマウスと比較したNOD/SCIDマウスでの腫瘍増殖抑制の程度はPDXの系統により大きく異なり,抗CD49b抗体で標識されるNK細胞の浸潤の程度と関連した。しかし,各種のNK細胞リガンドのPDX腫瘍細胞における発現と,NK細胞の浸潤度には関連を認めなかった。以上より,NK細胞による増殖抑制の程度は,乳がんPDX腫瘍により大きく異なることが示唆された。乳がんPDX組織へのNK細胞浸潤にかかわる分子機構については,さらなる検討が必要である。