The inhibition of pancreatic cancer progression by K-Ras-overexpressing mesenchymal stem cell-derived secretomes.
The inhibition of pancreatic cancer progression by K-Ras-overexpressing mesenchymal stem cell-derived secretomes.
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DOI：
10.1038/s41598-023-41835-6
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发表时间：
2023-09-12
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
胰腺导管腺癌（PDAC）是一种侵袭性癌症，生存率低。为了探索K-Ras原癌基因的未知功能，在间充质干细胞（MSC）中激活K-Ras，并检测MSC条件培养基（CM）对PDAC的影响。K-Ras的过表达提高了MSC中的PI 3 K信号传导，并且K-Ras/PI 3 K活化的MSC衍生的CM减少了肿瘤细胞的增殖和迁移，以及离体新鲜分离的人PDAC培养物的生长。CM的抗肿瘤能力与吉西他滨（一种治疗PDAC的常用化疗药物）相加。在小鼠模型中全身施用CM抑制PDAC在肺中的定殖。MSC CM富含Moesin（MSN），其通过与CD 44相互作用而充当细胞外肿瘤抑制蛋白。肿瘤抑制CM也产生PKA激活的外周血单核细胞。总的来说，这项研究表明，MSC CM可以通过激活K-Ras和PI 3 K而被工程化为肿瘤抑制剂，并且MSN-CD 44调节轴部分地负责PDAC治疗中的这种潜在的非常规选择。
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor survival. To explore an uncharted function of K-Ras proto-oncogene, K-Ras was activated in mesenchymal stem cells (MSCs) and the effects of MSC conditioned medium (CM) on PDAC were examined. Overexpression of K-Ras elevated PI3K signaling in MSCs, and K-Ras/PI3K-activated MSC-derived CM reduced the proliferation and migration of tumor cells, as well as the growth of ex vivo freshly isolated human PDAC cultures. CM’s anti-tumor capability was additive with Gemcitabine, a commonly used chemotherapeutic drug in the treatment of PDAC. The systemic administration of CM in a mouse model suppressed the colonization of PDAC in the lung. MSC CM was enriched with Moesin (MSN), which acted as an extracellular tumor-suppressing protein by interacting with CD44. Tumor-suppressive CM was also generated by PKA-activated peripheral blood mononuclear cells. Collectively, this study demonstrated that MSC CM can be engineered to act as a tumor-suppressive agent by activating K-Ras and PI3K, and the MSN-CD44 regulatory axis is in part responsible for this potential unconventional option in the treatment of PDAC.
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影响因子：
37.3
作者：
Keleg, Shereen;Buchler, Peter;Ludwig, Roman;Buchler, Markus W;Friess, Helmut
通讯作者：
Friess, Helmut
针对实体瘤中的KRAS：新型KRAS抑制剂的当前挑战和未来机会。
影响因子：
5.4
作者：
Indini A;Rijavec E;Ghidini M;Cortellini A;Grossi F
通讯作者：
Grossi F
影响因子：
5.2
作者：
Li KX;Sun X;Li BY;Yokota H
通讯作者：
Yokota H
影响因子：
29.4
作者：
Kanda M;Matthaei H;Wu J;Hong SM;Yu J;Borges M;Hruban RH;Maitra A;Kinzler K;Vogelstein B;Goggins M
通讯作者：
Goggins M
DOI：
10.3322/caac.21626
发表时间：
2020-09
期刊：
CA: a cancer journal for clinicians
影响因子：
--
作者：
Grossberg AJ;Chu LC;Deig CR;Fishman EK;Hwang WL;Maitra A;Marks DL;Mehta A;Nabavizadeh N;Simeone DM;Weekes CD;Thomas CR Jr
通讯作者：
Thomas CR Jr