Role of Inflammation in the Early Stages of Liver Metastasis

Spicer, Jonathan; Brodt, Pnina; Ferri, Lorenzo

doi:10.1007/978-94-007-0292-9_6

Cited by 12 publications

(18 citation statements)

References 135 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Neutrophils can also mediate tumor cell kill via antibody-dependent cellmediated cytotoxicity (ADCC) mechanisms (25) or by releasing cytolytic defensins that are abundant in neutrophil granules (reviewed in refs. 24,26).…”

Section: Cells Of the Hepatic Sinusoid Can Kill Tumor Cellsmentioning

confidence: 99%

See 1 more Smart Citation

The Multifaceted Role of the Microenvironment in Liver Metastasis: Biology and Clinical Implications

et al. 2013

Self Cite

View full text Add to dashboard Cite

The liver is host to many metastatic cancers, particularly colorectal cancer, for which the last 2 decades have seen major advances in diagnosis and treatment. The liver is a vital organ, and the extent of its involvement with metastatic disease is a major determinant of survival. Metastatic cells arriving in the liver via the bloodstream encounter the microenvironment of the hepatic sinusoid. The interactions of the tumor cells with hepatic sinusoidal and extrasinusoidal cells (endothelial, Kupffer, stellate, and inflammatory cells) determine their fate. The sinusoidal cells can have a dual role, sometimes fatal to the tumor cells but also facilitatory to their survival and growth. Adhesion molecules participate in these interactions and may affect their outcome. Bone marrowderived cells and chemokines also play a part in the early battle for survival of the metastases. Once the tumor cells have arrested and survived the initial onslaught, tumors can grow within the liver in 3 distinct patterns, reflecting differing host responses, mechanisms of vascularization, and proteolytic activity. This review aims to present current knowledge of the interactions between the host liver cells and the invading metastases that has implications for the clinical course of the disease and the response to treatment. Cancer Res; 73(7); 2031-43. Ó2013 AACR.

show abstract

Section: Cells Of the Hepatic Sinusoid Can Kill Tumor Cellsmentioning

confidence: 99%

“…Indeed, dynamic interactions between neutrophils and tumor cells that increase tumor cell invasiveness have been documented in vitro (reviewed in ref. 26). In vivo, neutrophils colocalize with cancer cells within the liver sinusoids, and their depletion causes a significant reduction in cancer cell arrest (48).…”

Section: The Dual Role Of Neutrophilsmentioning

confidence: 99%

The Multifaceted Role of the Microenvironment in Liver Metastasis: Biology and Clinical Implications

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Cancer is an inflammatory condition and the available treatments are associated with an acute inflammatory state, be it through tissue trauma, infectious complications, or tumor-mediated inflammation (3). A portion of this literature has focused on the clinical observation that elevated neutrophil counts or elevated neutrophil-to-lymphocyte ratios are predictive of poor outcomes and distant metastasis in patients with a wide array of epithelial malignancies including lung (4), gastric (5), ovarian (6), hepatic (6), pancreatic (7), and colon carcinomas (8).…”

Section: Introductionmentioning

confidence: 99%

“…The growing literature on neutrophilia in the perioperative period and, more specifically, in the pretreatment setting indicates that it is associated with poor oncologic outcomes. Inflammation arising from the primary tumor or from treatment-associated complications affect neutrophil function and numbers and may be related to cancer progression (3). Thus, an improved understanding of how neutrophils may participate in the metastatic cascade could provide new insight for patients who are eligible to receive therapies with curative intent.…”

Section: Introductionmentioning

confidence: 99%

“…The tissue manipulation required during surgery is associated with an important release of CTCs (27)(28)(29). Together, the combination of acute systemic inflammatory stimuli with high numbers of CTCs presents a fertile ground for the initiation of metastasis (3). The clinical evidence linking postoperative complications and high CTC numbers to poor oncologic outcomes is abundant (30)(31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neutrophils Promote Liver Metastasis via Mac-1–Mediated Interactions with Circulating Tumor Cells

et al. 2012

View full text Add to dashboard Cite

Although circulating neutrophils are associated with distant metastasis and poor outcome in a number of epithelial malignancies, it remains unclear whether neutrophils play an active causal role in the metastatic cascade. Using in vivo models of metastasis, we found that neutrophils promote cancer cell adhesion within liver sinusoids and, thereby, influence metastasis. Neutrophil depletion before cancer cell inoculation resulted in a decreased number of gross metastases in an intrasplenic model of liver metastasis. This effect was reversed when inflamed neutrophils were co-inoculated with cancer cells. In addition, early adhesion within liver sinusoids was inhibited in the absence of neutrophils and partially restored with a short perfusion of isolated activated neutrophils. Intravital microscopy showed that cancer cells adhered directly on top of arrested neutrophils, indicating that neutrophils may act as a bridge to facilitate interactions between cancer cells and the liver parenchyma. The adhesion of lipopolysaccharide-activated neutrophils to cancer cells was mediated by neutrophil Mac-1/ICAM-1. Our findings, therefore, show a novel role for neutrophils in the early adhesive steps of liver metastasis. Cancer Res; 72(16);

show abstract

Gram-positive pneumonia augments non-small cell lung cancer metastasisviahost toll-like receptor 2 activation

et al. 2017

View full text Add to dashboard Cite

Surgical resection of early stage nonsmall cell lung cancer (NSCLC) is necessary for cure. However, rates of postoperative bacterial pneumonias remain high and may confer an increased risk for metastasis. Toll-like receptors (TLRs) mediate the inflammatory cascade by recognizing microbial products at the surface of numerous cell types in the lung; however, little is known about how host TLRs influence NSCLC metastasis. TLR2 recognizes gram-positive bacterial cell wall components activating innate immunity. We demonstrate that lower respiratory tract infection with Streptococcus pneumonia augments the formation of murine H59 NSCLC liver metastases in C57BL/6 mice through host TLR2 activation. Infected mice demonstrate increased H59 and human A549 NSCLC adhesion to hepatic sinusoids in vivo compared with noninfected controls, a response that is significantly diminished in TLR2 knock-out mice. Intra-tracheal injection of purified TLR2 ligand lipoteichoic acid into mice similarly augments in vivo adhesion of H59 cells to hepatic sinusoids. Additionally, H59 and A549 NSCLC cells incubated with bronchoepithelial conditioned media show increased cell adhesion to extracellular matrix components in vitro and hepatic sinusoids in vivo in a manner that is dependent on bronchoepithelial TLR2 activation and interleukin-6 secretion. TLR2 is therefore a potential therapeutic target for gram-positive pneumonia-driven NSCLC metastasis.

show abstract

Role of Inflammation in the Early Stages of Liver Metastasis

Cited by 12 publications

References 135 publications

The Multifaceted Role of the Microenvironment in Liver Metastasis: Biology and Clinical Implications

The Multifaceted Role of the Microenvironment in Liver Metastasis: Biology and Clinical Implications

Neutrophils Promote Liver Metastasis via Mac-1–Mediated Interactions with Circulating Tumor Cells

Gram-positive pneumonia augments non-small cell lung cancer metastasisviahost toll-like receptor 2 activation

Contact Info

Product

Resources

About