The Role and Significance of Hepatic Environmental Cells in Tumor Metastatic Colonization to Liver

JIN Bei, ZHANG Ye-yu, PAN Jing-xuan

Abstract

Metastasis, a main cause of death in tumor patients, is a complicated process that involves multiple steps, presenting a major clinical challenge. Tumor cells break the physical boundaries of a primary tumor, intravasate into the lumina of blood vessels, travel around through blood circulation, extravasate into distant organs, colonize the host organs, and eventually develop into the foci of metastatic cancer. The metastasis of tumor cells exhibits organ-tropism, i.e., tumor cells preferentially spread to specific organs. Liver is a common site for metastasis. The pattern of metastasis in uveal melanoma, colorectal carcinoma, and pancreatic ductal adenocarcinoma shows organ-tropism for liver. The anatomical structure of liver determines its hemodynamic characteristics, e.g., low pressure and slow blood flow, which tend to facilitate the stasis and colonization of tumor cells in the liver. Besides the hemodynamic features, the metastatic colonization of liver depends largely on the interaction between tumor cells and the hepatic microenvironment (especially liver-resident cellular components). Resident cells of the hepatic microenvironment include hepatocytes, liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), Kupffer cells (KCs), etc. Herein, we discussed the role and significance of liver-resident cells in the metastatic colonization of tumor in the liver.

 

Keywords: Metastatic colonization of liver, Hepatocyte, Liver sinusoidal endothelial cells, Hepatic stellate cells, Kupffer cells

 

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References


TSILIMIGRAS D I， BRODT P， CLAVIEN P A， et al. Liver metastases. Nat Rev Dis Primers，2021，7(1): 27. doi: 10.1038/s41572-021-00261-6.

SHASHA T， GRUIJS M， Van EGMOND M， et al. Mechanisms of colorectal liver metastasis development. Cell Mol Life Sci，2022，79(12): 607. doi: 10.1007/s00018-022-04630-6.

AGUADO B A， BUSHNELL G G， RAO S S， et al. Engineering the pre-metastatic niche. Nat Biomed Eng，2017，1: 0077. doi: 10.1038/s41551-017-0077.

KAPLAN R N， RIBA R D， ZACHAROULIS S， et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature，2005，438(7069): 820–827. doi: 10.1038/nature04186.

WILLIAMSON T， SULTANPURAM N， SENDI H， et al. The role of liver microenvironment in hepatic metastasis. Clin Transl Med，2019， 8(1): 21. doi: 10.1186/s40169-019-0237-6.

WOHLFEIL S A， HAFELE V， DIETSCH B， et al. Hepatic endothelial notch activation protects against liver metastasis by regulating endothelial-tumor cell adhesion independent of angiocrine signaling. Cancer Res，2019，79(3): 598–610. doi: 10.1158/0008-5472.CAN-18-1752.

OLASO E， BENEDICTO A， LOPATEGI A， et al. A synthetic analog of resveratrol inhibits the proangiogenic response of liver sinusoidal cells during hepatic metastasis. Biomol Ther (Seoul)，2022，30(2): 162–169. doi: 10.4062/biomolther.2021.062.

ARTETA B， LASUEN N， LOPATEGI A， et al. Colon carcinoma cell interaction with liver sinusoidal endothelium inhibits organ-specific antitumor immunity through interleukin-1-induced mannose receptor in mice. Hepatology，2010，51(6): 2172–2182. doi: 10.1002/hep.23590.

ZUO Y， REN S， WANG M， et al. Novel roles of liver sinusoidal endothelial cell lectin in colon carcinoma cell adhesion, migration and in-vivo metastasis to the liver. Gut，2013，62(8): 1169–1178. doi: 10.1136/gutjnl-2011-300593.

BARBAZAN J， ALONSO-ALCONADA L， ELKHATIB N， et al. Liver metastasis is facilitated by the adherence of circulating tumor cells to vascular fibronectin deposits. Cancer Res，2017，77(13): 3431–3441. doi: 10.1158/0008-5472.CAN-16-1917.

Van den EYNDEN G G， MAJEED A W， ILLEMANN M， et al. The multifaceted role of the microenvironment in liver metastasis: biology and clinical implications. Cancer Res，2013，73(7): 2031–2043. doi: 10.1158/ 0008-5472.CAN-12-3931.

HUU HOANG T， SATO-MATSUBARA M， YUASA H， et al. Cancer cells produce liver metastasis via gap formation in sinusoidal endothelial cells through proinflammatory paracrine mechanisms. Sci Adv，2022， 8(39): eabo5525. doi: 10.1126/sciadv.abo5525.

JIN Y， ZHANG P， WANG Y， et al. Neddylation blockade diminishes hepatic metastasis by dampening cancer stem-like cells and angiogenesis in uveal melanoma. Clin Cancer Res，2018，24(15): 3741–3754. doi: 10. 1158/1078-0432.CCR-17-1703.

CARAMBIA A， FREUND B， SCHWINGE D， et al. TGF-beta-dependent induction of CD4(+)CD25(+)Foxp3(+) Tregs by liver sinusoidal endothelial cells. J Hepatol，2014，61(3): 594–599. doi: 10.1016/j.jhep.2014.04.027.

YU X， CHEN L， LIU J， et al. Immune modulation of liver sinusoidal endothelial cells by melittin nanoparticles suppresses liver metastasis. Nat Commun，2019，10(1): 574. doi: 10.1038/s41467-019-08538-x.

KHATIB A M， FALLAVOLLITA L， WANCEWICZ E V， et al. Inhibition of hepatic endothelial E-selectin expression by C-raf antisense oligonucleotides blocks colorectal carcinoma liver metastasis. Cancer Res，2002，62(19): 5393–5398.

QI M， FAN S， HUANG M， et al. Targeting FAPalpha-expressing hepatic stellate cells overcomes resistance to antiangiogenics in colorectal cancer liver metastasis models. J Clin Invest，2022，132(19): e157399. doi: 10.1172/JCI157399.

YONA S， KIM K W， WOLF Y， et al. Fate mapping reveals origins and dynamics of monocytes and tissue macrophages under homeostasis. Immunity，2013，38(1): 79–91. doi: 10.1016/j.immuni.2012.12.001.

WEN S W， AGER E I， CHRISTOPHI C， et al. Bimodal role of Kupffer cells during colorectal cancer liver metastasis. Cancer Biol Ther，2013， 14(7): 606–613. doi: 10.4161/cbt.24593.

TIMMERS M， VEKEMANS K， VERMIJLEN D， et al. Interactions between rat colon carcinoma cells and Kupffer cells during the onset of hepatic metastasis. Int J Cancer，2004，112(5): 793–802. doi: 10.1002/ijc. 20481.

MATSUMURA H， KONDO T， OGAWA K， et al. Kupffer cells decrease metastasis of colon cancer cells to the liver in the early stage. Int J Oncol， 2014，45(6): 2303–2310. doi: 10.3892/ijo.2014.2662.

COSTA-SILVA B， AIELLO N M， OCEAN A J， et al. Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat Cell Biol，2015，17(6): 816–826. doi: 10.1038/ncb3169.

HOSHINO A， COSTA-SILVA B， SHEN T L， et al. Tumour exosome integrins determine organotropic metastasis. Nature，2015，527(7578): 329–335. doi: 10.1038/nature15756.

SHIMIZU Y， AMANO H， ITO Y， et al. Angiotensin Ⅱ subtype 1a receptor signaling in resident hepatic macrophages induces liver metastasis formation. Cancer Sci，2017，108(9): 1757–1768. doi: 10.1111/cas.13306.

SUN H， MENG Q， SHI C， et al. Hypoxia-inducible exosomes facilitate liver-tropic premetastatic niche in colorectal cancer. Hepatology，2021， 74(5): 2633–2651. doi: 10.1002/hep.32009.

ZHAO S， MI Y， GUAN B， et al. Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer. J Hematol Oncol，2020，13(1): 156. doi: 10.1186/s13045- 020-00991-2.


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