Liver Regeneration Stimulates Tumor Metastases

Harun, Nadia; Nikfarjam, Mehrdad; Muralidharan, Vijayaragavan; Christophi, Christopher

doi:10.1016/j.jss.2006.06.024

Cited by 71 publications

(69 citation statements)

References 52 publications

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“…The factors related to the surgical stress itself represent transient changes, whereas the process of liver regeneration can act as a stronger and more sustained stimulus that promotes the growth of occult tumors and neoplastic development. Liver regeneration after surgery provides a microenvironment with many growth factors and cytokines that are favorable for tumorgenesis and tumor propagation through cell activation, proliferation, migration and angiogenesis [16,19,[24][25][26][27] . The majority of studies in HCC indicate that factors linked to tumor invasiveness and vascular involvement are the most important [20] .…”

Section: Regeneration Factors Influencing Tumor Growth and Metastasismentioning

confidence: 99%

“…Accumulating clinical and experimental studies have suggested that liver regeneration following surgical resection may activate occult micrometastases, facilitate tumor growth and thereby contribute to tumor recurrence [16,[24][25][26][27] . Similarly, an enhanced tumor growth rate has been reported following portal vein embolization when performed as a preparation to liver resection [28] .…”

Section: Introductionmentioning

confidence: 99%

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Effect of liver regeneration on malignant hepatic tumors

Shi

Line

2014

WJG

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Liver regeneration after major surgery may activate occult micrometastases and facilitate tumor growth, leading to liver tumor recurrence. Molecular changes during liver regeneration can provide a microenvironment that stimulates intrahepatic tumor propagation through alterations in cellular signaling pathways, where activation and proliferation of mature hepatocytes, hepatic progenitor cells, non-parenchymal liver cells might favor both liver regeneration and tumor growth. This review highlights recent advances of tumor growth and development in the regenerating liver, possible mechanisms and clinical implications. Key words: Hepatocellular carcinoma; Colorectal cancer; Recurrence; Liver regeneration; Hepatic progenitor cell; Epithelial to mesenchymal transition Core tip: The liver has a unique capacity for regeneration after cellular damage or partial removal of tissue, and modern liver surgery relies on this property. Liver regeneration is a complex process involving a large array of growth factors, cytokines and cells to restore hepatic mass and function. Experimental and clinical data indicate that the regeneration signals facilitate the growth of both primary and secondary liver tumors and can alter their malignant potential. This is an important mechanism underlying recurrence after liver surgery. New therapeutic strategies founded on better insight into the relationship between liver regeneration and tumor biology are needed.Shi JH, Line PD. Effect of liver regeneration on malignant hepatic tumors.

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Section: Regeneration Factors Influencing Tumor Growth and Metastasismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of liver regeneration on malignant hepatic tumors

Shi

Line

2014

WJG

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“…HGF-related c-Met pathway activation is critical for not only CRC progression, but also liver regeneration after hepatic resection. It has been feared that hepatectomy would induce tumor growth of the residual liver (27)(28)(29)(30), but no evidence for this has been demonstrated. Therefore, the present study was planned from the beginning to argue the advantages and disadvantages of surgical procedures for CRC liver metastasis.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of aggressive hepatectomy for colorectal liver metastasis, evaluated from the HGF/c-Met pathway

Matsui

Osada²,

Tomita³

et al. 2010

Int J Oncol

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Abstract. Liver metastasis is one of the most critical factors in deciding the prognosis of patients with colorectal cancer (CRC). Hepatectomy is the most curative treatment for liver metastasis of CRC. The high amount of hepatocyte growth factor (HGF) is produced to promote liver regeneration by hepatectomy. Theoretically, HGF produced after hepatectomy stimulates the progression of CRC cells with c-Met in residual liver. This study was aimed to evaluate the value of hepatectomy towards liver metastasis of CRC in relation to the HGF/c-Met pathway. Ninety-four patients with CRC (including 24 liver metastasis cases) were operated at Gifu University Hospital (2002)(2003)(2004). For these cases, the expression of c-Met in the primary and liver metastatic sites was evaluated by immunohistochemistry and Western blot. Experiments were also conducted on CT26 murine CRC cell line and a mouse liver metastasis model. In clinical study, the c-Met expression in liver metastatic sites was lower than in the primary sites in 87% of 24 cases. In basic study, the expression of c-Met protein in the liver tumor was significantly lower than in culture cells according to Western blot (p=0.033). The growth of residual liver tumors was not significantly different between 30% hepatectomy group and no operation group. The over-expression of c-Met was closely associated with CRC liver metastases. On the other hand, in liver metastatic lesions, the c-Met expression was reduced in comparison to primary lesions. Therefore, even if serum HGF levels increased due to liver resection during the regeneration period, residual liver metastases of CRC was not promoted in its progression. Aggressive hepatectomy would still be acceptable and favorable as a curative therapy.

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“…Only a short-term of angiogenesis burst can awaken a dormant tumor [15]. In fact, during the late phase of regeneration after PH, which mainly involves re-establishment of liver structure with angiogenesis, accelerations of tumor growth, and metastasis have been observed [12,16].…”

Section: Introductionmentioning

confidence: 99%

Angiogenesis: multiple masks in hepatocellular carcinoma and liver regeneration

Chen

Shi

et al. 2010

Hepatol Int

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Hepatocellular carcinoma (HCC) is naturally resistant to radiotherapy and cytotoxic chemotherapy, leaving surgery as the mainstream therapeutic approach. However, the 5-year recurrence rate after curative resection is as high as 61.5%. The background hepatitis B-or C-induced cirrhosis and the presence of micrometastases at the time of surgery have been regarded as two main causes of recurrence. Recently, accumulating evidence suggests that growth factors and cytokines released during the physiological process of post-surgical liver regeneration could induce the activation of dormant micrometastatic lesions. The establishment of neovasculature to support either liver regeneration or HCC growth involves multiple cell types including liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and circulating endothelial progenitors. The crosstalks among these cells are driven by multiple molecules and signaling pathways, including vascular endothelial growth factors and their receptors, platelet-derived growth factor, the angiopoietin/Tie family, hepatocyte growth factor/c-Met signaling, and others. Anti-angiogenic agent targeting liver cancer vasculature has been reported to be able to generate limited survival benefit of the patients. In this review, discussions are focused on various angiogenic mechanisms of HCC and liver regeneration, as well as the prevailing anti-angiogenic strategies.

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Liver Regeneration Stimulates Tumor Metastases

Cited by 71 publications

References 52 publications

Effect of liver regeneration on malignant hepatic tumors

Effect of liver regeneration on malignant hepatic tumors

Clinical significance of aggressive hepatectomy for colorectal liver metastasis, evaluated from the HGF/c-Met pathway

Angiogenesis: multiple masks in hepatocellular carcinoma and liver regeneration

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