The Effect of Starvation on Blood Stream Cancer Cell Metastasis to the Liver in Rat after Laparotomy

Muraoka, Tatsuya; Shirouzu, Kazuo; Ozasa, Hiroyuki; Oka, Yousuke; Momosaki, Kazuya; Iwakuma, Nobutaka; Tanaka, Katsuaki; Ishibashi, Nobuya

doi:10.2739/kurumemedj.ms63005

Cited by 7 publications

(4 citation statements)

References 31 publications

(30 reference statements)

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“…Considering with past reports, accumulated T cells in BM in SF mice could locally play a role as anti-leukemic immunosurveillance. Serum level of inflammatory cytokines such as TNFa and IL-1b was not upregulated even in SF group [21].…”

Section: •Discussionmentioning

confidence: 83%

Short-Term Fasting Induces Cell Cycle Arrest of Immature Hematopoietic Cells and Increases the Number of Naive T Cells in the Bone Marrow of Mice

Takakuwa

Nakashima

Koh

et al. 2016

Blood

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Calorie restriction has long been studied not only as a way to prolong longevity but also as an approach to improve cancer prevention and treatment. Dietary restriction may prevent senescence of the immune and hematopoietic systems. In addition, short-term fasting before chemotherapy can reduce hematological toxicity in cancer patients. We studied the influence of fasting on immune cells, hematopoietic stem cells, and progenitor cells in the bone marrow and spleen of mice. Six-to-twelve-week old C57BL/6 mice were starved for 48 hours before analysis. We collected bone marrow and splenic cells from starved and control mice. After 48 hours of fasting, the body weight significantly decreased by an average of 24.1% compared to that of normal control mice. Calorie restriction caused a significant decrease in peripheral white blood cell count by an average of 48.3%, but hemoglobin level and platelet count were less affected. The averaged total number of bone marrow cells in the fasting group was significantly lower than that in the normal control group (2.45×107 versus 3.14×107, P < 0.01). In fasted mice there was a significant reduction in the hematopoietic stem cell count, using detection based on the lineage- c-kit+ Sca-1+, compared to control mice (0.83×105 versus 1.24×105, P < 0.05). In contrast, there was no significant difference for progenitor cells detected based on the lineage- c-kit+ Sca-1- (6.81×105 versus 7.75×105, P = 0.11). We performed colony assays with bone marrow cells from fasted and control mice. There was no difference between the two groups for not only the primary colony assay but also for the secondary and tertiary assays. Annexin V and 7-AAD analysis by flow cytometry showed that the rates of early and late apoptosis were almost identical in hematopoietic stem cells and progenitor cells, on comparing fasted and control mice. Furthermore, DNA cell cycle analysis of progenitor cells showed that short-term fasting caused a significant increase in the percentage in G0/G1 phase (83.1% versus 70.7%, P < 0.05) and decreases in the S and G2/M phases. These results imply that immature bone marrow cells retained their proliferative capacity by maintaining cell cycle arrest after short-term fasting, a finding that may account for the protective effect of starvation against chemotherapy in cancer patients. Calorie restriction caused a significant decrease in B cells in bone marrow (5.38×106 versus 8.1×106, P < 0.05) and especially in the spleen (6.65×106 versus 33.0×106, P < 0.001), and also significantly decreased T cells in the spleen (3.91×106 versus 14.5×106, P < 0.01). To our surprise, we detected a remarkable increase in the number of T cells in the bone marrow of fasted mice (1.25×106 versus 0.91×106, P < 0.01). Of greatest significance CD44- naive CD8+ T cells were dramatically increased in fasted bone marrow (1.74×106 versus 0.47×106, P < 0.01), and CD44- naive CD4+ T cells were also increased (0.23×106 versus 0.07×106, P < 0.05). In contrast, the numbers of CD62L- CD44+ effector memory and CD62L+ CD44+central memory T cells were not substantially changed after starvation. The increased naive T cells had no activated markers and appear to have migrated into bone marrow in a resting state without proliferating there. Short-term fasting decreased the number of hematopoietic stem cells but progenitor cells remained in a relatively quiescent state, with a prolonged DNA cell cycle and retention of colony-forming capabilities. The number of T cells in the bone marrow of fasted mice also increased dramatically, especially naive CD8+ T cells which probably migrated in from other lymphoid tissues. These findings imply that immature hematopoietic cells and some lymphoid cells can survive starvation while maintaining their function. The mechanisms by which T lymphoid cells promptly accumulate in bone marrow during starvation are under investigation. Disclosures Koh: Pfizer: Consultancy, Honoraria. Nakane:Mundipharma KK: Research Funding. Nakamae:Mochida Pharmaceutical Co., Ltd.: Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis Pharma KK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel/accommodation/meeting expenses, Research Funding. Hino:Nippon Shinyaku: Honoraria, Speakers Bureau; Pfizer: Honoraria, Research Funding; Alexion: Honoraria, Research Funding.

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Section: •Discussionmentioning

confidence: 83%

Short-Term Fasting Induces Cell Cycle Arrest of Immature Hematopoietic Cells and Increases the Number of Naive T Cells in the Bone Marrow of Mice

Takakuwa

Nakashima

Koh

et al. 2016

Blood

View full text Add to dashboard Cite

show abstract

“…Considering past reports, accumulated T cells in BM in SF mice could locally play a role as antileukemic immunosurveillance. The serum levels of inflammatory cytokines such as TNFα and IL-1β were not upregulated even in the SF group [21]. …”

Section: Discussionmentioning

confidence: 99%

Short-Term Fasting Induces Cell Cycle Arrest in Immature Hematopoietic Cells and Increases the Number of Naïve T Cells in the Bone Marrow of Mice

et al. 2019

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Calorie restriction (CR) has been studied as a way to prolong longevity, and CR before chemotherapy can reduce hematological toxicity in cancer patients. We investigated the influence of fasting on immune cells and immature hematopoietic cells. In fasted mice, there was a significant reduction in the hematopoietic stem cell count but no significant difference for progenitor cells. Colony assays showed no difference and the rates of early and late apoptosis were almost identical when comparing fasted and control mice. DNA cell cycle analysis of immature bone marrow (BM) cells showed that CR caused a significant increase in the percentage in the G0/G1 phase and decreases in the S and G2/M phases. We detected a remarkable increase of T cells in the BM of fasted mice. CD44– naïve CD8+ T cells were more numerous in fasted BM, as were naïve CD4+ T cells, and part of those T cells showed less tendency in the G0/G1 phase. Immature hematopoietic cells remained in a relatively quiescent state and retention of colony-forming capacity during CR. The number of naïve T cells in the BM of fasted mice increased. These findings imply immature hematopoietic cells and some lymphoid cells can survive starvation, whilst maintaining their function.

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“…В настоящее время используют два основных способа моделирования метастазирования. Первый из них -экспериментальный, или искусственный, включает в себя модели, в которых опухолевые клетки вводятся непосредственно в орган или вены [10,14,17,21]. При внутрисосудистом введении опухолевые клетки проникают в капиллярное русло и создают сайты экспериментальных метастазов в том органе, в региональный сосуд которого они попали, например печень, легкие [2,14].…”

Section: моделирование метастазированияunclassified

Methods of Experimental Modeling of Metastasis

et al. 2021

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One of the main problems of modern medicine is cancer, which is the second leading cause of death after cardiovascular disease. Malignant neoplasms have been known for a long time; however, their study still presents signiﬁcant difﬁculties. Modeling of malignant processes in animals allow researchers to study tumors and the main patterns of malignant growth characteristic of animals and humans. The main cause of death in malignant neoplasms is the process of metastasis formation, which remains to be understood in detail. The study of metastatic processes is one of the most important tasks of oncology. To this end, various models of tumor metastasis are created. The article reviews literature data on the most popular models of metastasis in experimental conditions. The advantages and disadvantages of the main approaches to modeling metastasis are evaluated.

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The Effect of Starvation on Blood Stream Cancer Cell Metastasis to the Liver in Rat after Laparotomy

Abstract: Preoperative malnutrition by 48 hours starvation reduced inflammatory cytokine response and cellular immunity, resulting in an increase in hematogenous liver metastasis.

Cited by 7 publications

References 31 publications

Short-Term Fasting Induces Cell Cycle Arrest of Immature Hematopoietic Cells and Increases the Number of Naive T Cells in the Bone Marrow of Mice

Short-Term Fasting Induces Cell Cycle Arrest of Immature Hematopoietic Cells and Increases the Number of Naive T Cells in the Bone Marrow of Mice

Short-Term Fasting Induces Cell Cycle Arrest in Immature Hematopoietic Cells and Increases the Number of Naïve T Cells in the Bone Marrow of Mice

Methods of Experimental Modeling of Metastasis

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