Premalignant pancreatic cells seed stealth metastasis in distant organs in mice
Premalignant pancreatic cells seed stealth metastasis in distant organs in mice
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癌前胰腺细胞在小鼠远处器官中隐匿转移
DOI：
10.1038/s41388-021-01706-8
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发表时间：
2021
期刊：
影响因子：
8
通讯作者：
Masato Nagino
中科院分区：
文献类型：
--
作者：
Junpei Yamaguchi;Toshio Kokuryo;Yukihiro Yokoyama;Tomoki Ebata;Yosuke Ochiai;Masato Nagino
最近的研究表明，肿瘤细胞的传播发生在乳腺癌和胰腺癌发生的早期阶段，这被称为早期传播。早期播散的证据主要在血流和骨髓中得到证实;然而，有限的证据揭示了远处器官中播散细胞的存在和行为。在这里，我们表明，癌前胰腺细胞种子远距离隐形转移，最终发展成明显的转移。通过分析谱系标记的胰腺癌小鼠模型（KPCT/TFF 1 KO; Pdx 1-Cre/LSL-KRASG 12 D/LSL-p53 R172 H/LSL-tdTomato/TFF 1 KO），我们发现癌前胰腺细胞，而不是成熟的恶性细胞，更容易进入血液并驻留在骨髓、肝脏和肺中。虽然这些转移性细胞表现出宿主器官细胞的特征，并且不表现为恶性细胞，但它们发生恶性转化并形成独特的肿瘤。令人惊讶的是，远处转移的表现甚至发生在原发部位的肿瘤发展之前。我们的数据显示，播散性癌前病变细胞悄悄地驻留在远处器官中，并与原发性肿瘤的进展平行发展。这些观察结果表明，我们必须重建转移性胰腺癌的治疗策略。
Recent findings suggest that the dissemination of tumor cells occurs at the early stage of breast and pancreatic carcinogenesis, which is known as early dissemination. The evidence of early dissemination has been demonstrated predominantly in the bloodstream and bone marrow; however, limited evidence has revealed the existence and behavior of disseminated cells in distant organs. Here, we show that premalignant pancreatic cells seed distant stealth metastasis that eventually develops into manifest metastasis. By analyzing lineage-labeled pancreatic cancer mouse models (KPCT/TFF1KO; Pdx1-Cre/LSL-KRASG12D/LSL-p53R172H/LSL-tdTomato/TFF1KO), we found that premalignant pancreatic cells, rather than mature malignant cells, were prone to enter the bloodstream and reside in the bone marrow, liver, and lung. While these metastatic cells exhibited the characteristics of the cells of host organs and did not behave as malignant cells, they underwent malignant transformation and formed distinct tumors. Surprisingly, the manifestation of distant metastasis occurred even before tumor development in the primary site. Our data revealed that disseminated premalignant cells reside stealthily in distant organs and evolve in parallel with the progression of the primary tumor. These observations suggest that we must rebuild a therapeutic strategy for metastatic pancreatic cancer.
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影响因子：
29.4
作者：
Rhim AD;Thege FI;Santana SM;Lannin TB;Saha TN;Tsai S;Maggs LR;Kochman ML;Ginsberg GG;Lieb JG;Chandrasekhara V;Drebin JA;Ahmad N;Yang YX;Kirby BJ;Stanger BZ
通讯作者：
Stanger BZ
影响因子：
50.3
作者：
Hingorani, SR;Petricoin, EF;Tuveson, DA
通讯作者：
Tuveson, DA
影响因子：
11.2
作者：
Ao, Zheng;Shah, Sanket H.;El-Ashry, Dorraya
通讯作者：
El-Ashry, Dorraya
影响因子：
50.3
作者：
Kang Y;Pantel K
通讯作者：
Pantel K