scholarly journals Immunoregulatory Monocyte Subset Promotes Metastasis Associated With Therapeutic Intervention for Primary Tumor

2021 ◽  
Vol 12 ◽  
Author(s):  
Takumi Shibuya ◽  
Asami Kamiyama ◽  
Hirotaka Sawada ◽  
Kenta Kikuchi ◽  
Mayu Maruyama ◽  
...  
Keyword(s):  
Lung Metastasis ◽  
Therapeutic Intervention ◽  
Primary Tumor ◽  
Tissue Repair ◽  
Target Cells ◽  
Monocyte Subset ◽  
Local Inflammation ◽  
Cxcr4 Antagonist ◽  
Metastatic Recurrence ◽  
Metalloproteinase 9

Systemic and local inflammation associated with therapeutic intervention of primary tumor occasionally promotes metastatic recurrence in mouse and human. However, it remains unclear what types of immune cells are involved in this process. Here, we found that the tissue-repair-promoting Ym1+Ly6Chi monocyte subset expanded as a result of systemic and local inflammation induced by intravenous injection of lipopolysaccharide or resection of primary tumor and promoted lung metastasis originating from circulating tumor cells (CTCs). Deletion of this subset suppressed metastasis induced by the inflammation. Furthermore, transfer of Ym1+Ly6Chi monocytes into naïve mice promoted lung metastasis in the mice. Ym1+Ly6Chi monocytes highly expressed matrix metalloproteinase-9 (MMP-9) and CXCR4. MMP-9 inhibitor and CXCR4 antagonist decreased Ym1+Ly6Chi-monocyte-promoted lung metastasis. These findings indicate that Ym1+Ly6Chi monocytes are therapeutic target cells for metastasis originating from CTCs associated with systemic and local inflammation. In addition, these findings provide a novel predictive cellular biomarker for metastatic recurrence after intervention for primary tumor.

Peptides of Tetraspanin Oncoprotein CD151 Trigger Active Immunity Against Primary Tumor and Experimental Lung Metastasis

2019 ◽  
Author(s):  
Wanzun Lin ◽  
Jun Liu ◽  
Juhui Chen ◽  
Jiancheng Li ◽  
Sufang Qiu ◽  
...  
Keyword(s):  
Lung Metastasis ◽  
Primary Tumor ◽  
Active Immunity

scholarly journals Lung Metastasis Mimicking Fingertip Infection

2015 ◽  
Vol 2015 ◽  
pp. 1-3
Author(s):  
Salih Soylemez ◽  
Murat Demiroglu ◽  
Mehmet Ali Yayla ◽  
Korhan Ozkan ◽  
Bugra Alpan ◽  
...  
Keyword(s):  
Surgical Treatment ◽  
Life Expectancy ◽  
Medical History ◽  
Lung Metastasis ◽  
Primary Tumor ◽  
Poor Prognosis ◽  
Past Medical History

Metastasis fingers (acral metastasis) are finding a poor prognosis. Past medical history should be questioned and metastasis from primary tumor should be kept in mind in patients with pain, swelling, and hyperemia in fingers. Successful surgical treatment on acral metastasis does not extend the life expectancy; however, it reduces the patient’s pain during his terminal period, saves the functions of the limb, and increases life comfort.

Lung metastasis as predictor for prognosis in metastatic colorectal cancer with mutated KRAS.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 636-636
Author(s):  
Ben Boursi ◽  
Einat shacham-Shmueli ◽  
Yaacov Richard Lawrence ◽  
Yu-Xiao Yang ◽  
Kim Anna Reiss ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Liver Metastasis ◽  
Metastatic Colorectal Cancer ◽  
Lung Metastasis ◽  
Primary Tumor ◽  
Clinical Decision Making ◽  
Secondary Analysis ◽  
Tumor Location ◽  
Single Site ◽  
Primary Tumor Location

636 Background: Previous studies have shown that prognosis in metastatic colorectal cancer (mCRC) may vary according to sites of metastasis. We evaluated prognosis in individuals with single site metastasis, according to several clinical and genetic variables. Methods: Using the National Cancer Database we identified 58,044 mCRC patients with a synchronous single site of metastasis. We first examined the effect of metastasis site on prognosis. In a secondary analysis, among individuals who had not undergone surgery or received radiotherapy, we examined the prognostic value of chemotherapy intensity, KRAS status, primary tumor location and CEA levels. Results: Individuals with lung metastasis had the best prognosis (HR = 0.80, 0.77-0.83), followed by those with liver metastasis (HR = 1.11, 1.07-1.15), while those with bone or brain metastasis had the worse prognosis. In a subgroup analysis, we assessed prognosis among individuals who received multi-agent chemotherapy and had not undergone surgery or received radiotherapy. Individuals with lung metastasis and mutant KRAS had better prognosis compared with those with liver metastasis, (HR = 0.69, 0.54-0.88), regardless of primary tumor location or CEA levels. Conclusions: Single site metastasis to the lungs is associated with better prognosis in mCRC, specifically among KRAS mutant tumors. This survival advantage should be taken into consideration in clinical decision-making.

Effect of general anesthetics on the tumor micro-environment in mouse models of breast cancers of spontaneous metastasis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15503-e15503
Author(s):  
Jun Lin ◽  
Ru Li ◽  
Yujie Huang
Keyword(s):  
Breast Cancer ◽  
Mouse Models ◽  
Lung Metastasis ◽  
Primary Tumor ◽  
Cancer Metastasis ◽  
Metastatic Breast ◽  
Health Concern ◽  
Breast Cancers ◽  
General Anesthetics ◽  
Primary Tumors

e15503 Background: Metastatic breast cancer is a pressing health concern worldwide. Various treatments have been developed but no significant long-term changes in overall survival are observed. Therefore, there is a demand to improve current therapies to treat this disease. Surgical resection of the primary tumors is essential in the treatment. However, accumulating evidence alludes to a role for volatile anesthetics which are used during the surgery in metastatic tumor development, but the mechanism remains largely unknown. We have shown anesthetics exert different effects on lung metastasis in mouse models of breast cancers. This study analyses the effect of general anesthetics in lung microenvironment associated with the increased metastases. Methods: Balb/c mice and NOD-SCID mice were orthotopically implanted with 4T1 cells and MDA-MB-231 cells respectively, in the mammary fat pad to generate primary tumors. Mice were subjected to the tested anesthetic during implantation and/or before and after surgery. Surgical dissection of primary tumor was performed under anesthesia with sevoflurane or an intravenous anesthetic propofol. Survival curve was constructed and analysed. Mice were euthanized to harvest tissues for histology and cell analysis. Results: As we previously reported, surgical dissection of primary tumor in mice under anesthesia with sevoflurane led to significantly more lung metastasis than with propofol in both syngeneic murine 4T1 and xenograft human MDA-MB-231 breast cancer models. Sevoflurane was associated with increased IL6(Li, Huang, & Lin, 2020). Here we show that anesthesia with sevoflurane resulted in changes of stroma composition in the lung, which was reversed by IL6 pathway interruption. Conclusions: Those results contribute to our understanding of effects of sevoflurane on cancer metastasis and suggest a potential therapeutic approach to overcome the risk of general anesthesia. Li, R., Huang, Y., & Lin, J. (2020). Distinct effects of general anesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse models. Nat Commun, 11, 642.

scholarly journals Novel blood test to predict neoplastic activity in healthy patients and metastatic recurrence after primary tumor resection

2016 ◽  
Vol 5 ◽  
pp. 184945441666366 ◽  
Author(s):  
Mohamed Abdouh ◽  
Dana Hamam ◽  
Vincenzo Arena ◽  
Manuel Arena ◽  
Hussam Alamri ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Blood Test ◽  
Tumor Resection ◽  
Primary Tumor Resection ◽  
Metastatic Recurrence

scholarly journals Host deficiency in ephrin-A1 inhibits breast cancer metastasis

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 217 ◽  
Author(s):  
Eileen Shiuan ◽  
Ashwin Inala ◽  
Shan Wang ◽  
Wenqiang Song ◽  
Victoria Youngblood ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cell ◽  
Lung Metastasis ◽  
Primary Tumor ◽  
Tumor Recurrence ◽  
Cancer Metastasis ◽  
Primary Tumor Growth ◽  
Primary Tumors ◽  
4T1 Cells

Background: The conventional dogma of treating cancer by focusing on the elimination of tumor cells has been recently refined to include consideration of the tumor microenvironment, which includes host stromal cells. Ephrin-A1, a cell surface protein involved in adhesion and migration, has been shown to be tumor suppressive in the context of the cancer cell. However, its role in the host has not been fully investigated. Here, we examine how ephrin-A1 host deficiency affects cancer growth and metastasis in a murine model of breast cancer. Methods: 4T1 cells were orthotopically implanted into the mammary fat pads or injected into the tail veins of ephrin-A1 wild-type (Efna1+/+), heterozygous (Efna1+/-), or knockout (Efna1-/-) mice. Tumor growth, lung metastasis, and tumor recurrence after surgical resection were measured. Flow cytometry and immunohistochemistry (IHC) were used to analyze various cell populations in primary tumors and tumor-bearing lungs. Results: While primary tumor growth did not differ between Efna1+/+, Efna1+/-, and Efna1-/- mice, lung metastasis and primary tumor recurrence were significantly decreased in knockout mice. Efna1-/- mice had reduced lung colonization of 4T1 cells compared to Efna1+/+ littermate controls as early as 24 hours after tail vein injection. Furthermore, established lung lesions in Efna1-/- mice had reduced proliferation compared to those in Efna1+/+ controls. Conclusions: Our studies demonstrate that host deficiency of ephrin-A1 does not impact primary tumor growth but does affect metastasis by providing a less favorable metastatic niche for cancer cell colonization and growth. Elucidating the mechanisms by which host ephrin-A1 impacts cancer relapse and metastasis may shed new light on novel therapeutic strategies.

scholarly journals C-Kit, a Double-Edged Sword in Liver Regeneration and Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Weina Wang ◽  
Liyan Shui ◽  
Yanning Liu ◽  
Min Zheng
Keyword(s):  
Liver Regeneration ◽  
Tissue Repair ◽  
Critical Role ◽  
Signal Transduction Pathway ◽  
Basic Research ◽  
Target Cells ◽  
Oval Cells ◽  
Transduction Pathway ◽  
Stromal Tumors

Previous studies have reported an important role of c-kit in embryogenesis and adulthood. Activation of the SCF/KIT signal transduction pathway is customarily linked to cell proliferation, migration and survival thus influence hematopoiesis, pigmentation, and spermatogenesis. The role of c-kit in the liver is controversial, it is however argued that it is a double-edged sword in liver regeneration and diseases. First, liver c-kit+ cells, including oval cells, bile epithelial cells, and part of hepatocytes, participate in liver tissue repair by regenerating target cells according to the type of liver injury. At the same time, c-kit+ mast cells, act as immature progenitors in circulation, playing a critical role in liver fibrosis. Furthermore, c-kit is also a proto-oncogene. Notably, c-kit overexpression regulates gastrointestinal stromal tumors. Various studies have explored on c-kit and hepatocellular carcinoma, nevertheless, the intricate roles of c-kit in the liver are largely understudied. Herein, we extensively summarize previous studies geared toward providing hints for future clinical and basic research.

scholarly journals Rewiring PBMC responses to prevent CHIKV infection-specific monocyte subset redistribution and cytokine responses

2020 ◽  
Author(s):  
José Alberto Aguilar-Briseño ◽  
Mariana Ruiz Silva ◽  
Jill Moser ◽  
Mindaugas Pauzuolis ◽  
Jolanda M. Smit ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Inflammatory Responses ◽  
Chronic Arthritis ◽  
Target Cells ◽  
Monocyte Subset ◽  
Chikv Infection ◽  
Peripheral Blood Mononuclear ◽  
Vitro Model

AbstractInfection with the mosquito-borne Chikungunya virus (CHIKV) causes acute or chronic arthritis in humans. Inflammatory responses mediated by monocytes, the primary target cells of CHIKV infection in the blood, are considered to play an important role in CHIKV pathogenesis. A recent study revealed that the acute phase of CHIKV infection is characterized by a monocyte-driven response, with an expansion of the intermediate monocyte (IM) subset. In this study, we adopted a previously established in vitro model of CHIKV infection in peripheral blood mononuclear cells, to elucidate the mechanism and relevance of IM expansion in CHIKV replication and associated inflammatory responses. Our data show that infectious but not replication-incompetent CHIKV increases the frequency of IM and to a lesser extent, non-classical (NM) monocytes while reducing the number of classical monocytes (CM). The increase of IM or NM frequency coincided with the activation of inflammatory response and occurred in the absence of lymphocytes implying that monocyte-derived cues are sufficient to drive this effect. Importantly, priming of monocytes with LPS prevented expansion of IM and NM but had no effect on viral replication. It did however alter CHIKV-induced cytokine signature. Taken together, our data delineate the role of IM in CHIKV infection-specific innate immune responses and provide insight for the development of therapeutic strategies that may focus on rewiring monocyte immune responses to prevent CHIKV-mediated arthralgia and arthritis.

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