Circulating tumor cells promote the metastatic colonization of disseminated carcinoma cells by inducing systemic inflammation

Li, Yongchao; Zou, Jiu-Ming; Luo, Chao; Shu, Yu; Luo, Jing; Qin, Jian; Wang, Yu; Liu, Dong; Wang, Shanshan; Chi, Gang; Guo, Fang; Zhang, Guimei; Feng, Zuo-Hua

doi:10.18632/oncotarget.16084

Cited by 31 publications

(21 citation statements)

References 57 publications

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“…It was documented recently (20) that even a minimal number of circulating tumour cells elicit a systemic inflammatory status contributing to the promotion of tumour metastasis. These circulating tumour cells represent a clinically undetectable disease burden.…”

Section: Introductionmentioning

confidence: 99%

Serum proteomic analysis of melanoma patients with immunohistochemical profiling of primary melanomas and cultured cells: Pilot study

et al. 2019

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The steadily increasing incidence of malignant melanoma (MM) and its aggressive behaviour makes this tumour an attractive cancer research topic. The tumour microenvironment is being increasingly recognised as a key factor in cancer biology, with an impact on proliferation, invasion, angiogenesis and metastatic spread, as well as acquired therapy resistance. Multiple bioactive molecules playing cooperative roles promote the chronic inflammatory milieu in tumours, making inflammation a hallmark of cancer. This specific inflammatory setting is evident in the affected tissue. However, certain mediators can leak into the systemic circulation and affect the whole organism. The present study analysed the complex inflammatory response in the sera of patients with MM of various stages. Multiplexed proteomic analysis (Luminex Corporation) of 31 serum proteins was employed. These targets were observed in immunohistochemical profiles of primary tumours from the same patients. Furthermore, these proteins were analysed in MM cell lines and the principal cell population of the melanoma microenvironment, cancer-associated fibroblasts. Growth factors such as hepatocyte growth factor, granulocyte-colony stimulating factor and vascular endothelial growth factor, chemokines RANTES and interleukin (IL)-8, and cytokines IL-6, interferon-α and IL-1 receptor antagonist significantly differed in these patients compared with the healthy controls. Taken together, the results presented here depict the inflammatory landscape that is altered in melanoma patients, and highlight potentially relevant targets for therapy improvement.

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Section: Introductionmentioning

confidence: 99%

Serum proteomic analysis of melanoma patients with immunohistochemical profiling of primary melanomas and cultured cells: Pilot study

et al. 2019

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“…IL-37 was able to suppress CTC-induced conversion of neutrophil function to pro-tumor phenotype. These findings suggest anti-inflammatory therapy could be used when higher CTC count is detected 66…”

Section: Extravasation and Colonization Of Distant Tissuesmentioning

confidence: 85%

“…Another factor might be the induction of inflammation, as described by the De Cock et al 65. In 2017, a Chinese study similarly reported that CTC-mediated systemic inflammation and neutrophil recruitment to pre-metastatic tissues is the mechanism of metastatic colonization by the CTCs 66. This was demonstrated in vitro using an anti-inflammatory cytokine interleukin 37 (IL-37) to deplete neutrophils, suppress inflammatory response and thus the promoting effect of CTCs on tumor metastasis 66.…”

Section: Extravasation and Colonization Of Distant Tissuesmentioning

confidence: 99%

“…In 2017, a Chinese study similarly reported that CTC-mediated systemic inflammation and neutrophil recruitment to pre-metastatic tissues is the mechanism of metastatic colonization by the CTCs 66. This was demonstrated in vitro using an anti-inflammatory cytokine interleukin 37 (IL-37) to deplete neutrophils, suppress inflammatory response and thus the promoting effect of CTCs on tumor metastasis 66. The mechanism is based on the assumption of functional plasticity of neutrophils in the tumor microenvironment.…”

Section: Extravasation and Colonization Of Distant Tissuesmentioning

confidence: 99%

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The biology and clinical potential of circulating tumor cells

Ložar

Geršak

Čemažar

et al. 2019

Radiology and Oncology

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Background Tumor cells can shed from the tumor, enter the circulation and travel to distant organs, where they can seed metastases. These cells are called circulating tumor cells (CTCs). The ability of CTCs to populate distant tissues and organs has led us to believe they are the primary cause of cancer metastasis. The biological properties and interaction of CTCs with other cell types during intravasation, circulation in the bloodstream, extravasation and colonization are multifaceted and include changes of CTC phenotypes that are regulated by many signaling molecules, including cytokines and chemokines. Considering a sample is readily accessible by a simple blood draw, monitoring CTC levels in the blood has exceptional implications in oncology field. A method called the liquid biopsy allows the extraction of not only CTC, but also CTC products, such as cell free DNA (cfDNA), cell free RNA (cfRNA), microRNA (miRNA) and exosomes. Conclusions The clinical utility of CTCs and their products is increasing with advances in liquid biopsy technology. Clinical applications of liquid biopsy to detect CTCs and their products are numerous and could be used for screening of the presence of the cancer in the general population, as well as for prognostic and predictive biomarkers in cancer patients. With the development of better CTC isolation technologies and clinical testing in large prospective trials, increasing clinical utility of CTCs can be expected. The understanding of their biology and interactions with other cell types, particularly with those of the immune system and the rise of immunotherapy also hold great promise for novel therapeutic possibilities.

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“…It is still largely unknown and is a subject of debate for the mechanisms determining the metastatic cell fate. Drawing inspiration from literature that transplantation of metastatic tumor cells to mice can lead to enrichment and augment in metastasis 10 , 12 , 13 , we established a bone-metastatic triple-negative breast cancer cell subline by transplanting a widely-used cell line, MDA-MB-231, to the fad pat of female nude mice to grow tumors in vivo . The bone metastatic cell sublines exhibited higher rate of proliferation, migration, invasion and bone metastasis.…”

Section: Introductionmentioning

confidence: 99%

Cancer stem cell property and gene signature in bone-metastatic Breast Cancer cells

Luo¹,

Xu²,

Li³

et al. 2020

Int. J. Biol. Sci.

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The majority of the deaths from breast cancer is due to metastasis. Bone is the most common organ to which breast cancer cells metastasize. The mechanism regulating the bone-metastatic preference remains unclear; there is a lack of a gene signature to distinguish bone-metastatic breast cancer cells. Herein, florescence-labeled MDA-MB-231 cells were transplanted into the fat pads of of the mammary gland in nude mice to generate breast tumors. Tumor cells invaded into the circulation were tracked by in vivo flow cytometry system. Metastatic tumor cells in the bone were isolated using fluorescent-activated cell sorting technique, followed by assays of cell colony formation, migration and invasion, mammosphere formation in vitro, mammary gland tumorigenesis in vivo, and Next-Generation Sequencing analysis as well. Through tumor regeneration and cell sorting, two bone-metastatic cell sublines were derived from MDA-MB-231 cells; which showed higher abilities to proliferate, migrate, invade and epithelial-to-mesenchymal transit in vitro, and stronger ability to regenerate tumors and metastasize to the bone in vivo. Both cell sublines exhibited cancer stem cell-like characteristics including higher expression levels of stem cell markers and stronger ability for mommaspheres formation. Furthermore, a Normal Distribution-like pattern of the bone-metastatic cells invading into circulation was firstly identified. Deep-sequencing analysis indicated upregulation of multiple signaling pathways in regulating EMT, cell membrane budding and morphologic change, lipid metabolism, and protein translation, which are required to provide adequate metabolic enzymes, structural proteins, and energy for the cells undergoing metastasis. In conclusion, we established two bone-metastatic breast cancer cell sublines, carrying higher degree of stemness and malignancy. The gene signature distinguishing the bone-metastatic breast cancer cells holds therapeutic potentials in prevention of breast cancer metastasis to the bone.

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Circulating tumor cells promote the metastatic colonization of disseminated carcinoma cells by inducing systemic inflammation

Cited by 31 publications

References 57 publications

Serum proteomic analysis of melanoma patients with immunohistochemical profiling of primary melanomas and cultured cells: Pilot study

Serum proteomic analysis of melanoma patients with immunohistochemical profiling of primary melanomas and cultured cells: Pilot study

The biology and clinical potential of circulating tumor cells

Cancer stem cell property and gene signature in bone-metastatic Breast Cancer cells

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