• Journal of Microbiology and Biotechnology
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• v.8 no.1
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• pp.74-80
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• 1998

CS-2l lymphoma cells that preferentially metastasize to lymph nodes after s.c. inoculation into BALB/c mice were grown in vitro in the presence of CA- 12 stromal cells isolated from lymph nodes. In order to obtain fundamental data on the identification and characterization of the soluble factors produced by CA-12 stromal cells, the conditioned medium of CA-12 stromal cells that inhibited apoptosis of CS-21 cells was examined. Various analytical treatments revealed that the soluble factors in CA-12 conditioned medium are very sensitive to heat treatment and trypsinization. Moreover CA-12 conditioned medium has an affinity with heparin but not with Con-A. In addition to these, the activity of CA-12 conditioned medium was blocked by H-7, a PKC inhibitor, but the conditioned medium could not induce the differentiation of thymocytes. We concluded that CA-12 conditioned medium contains stromal cell-derived apoptosis-inhibitory molecules that play an important role in proliferation of CS-2l cells by suppressing cell apoptosis.

• Journal of Veterinary Science
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• v.22 no.3
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• pp.25.1-25.16
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• 2021

Background: Malignant lymphoma is the most common hematopoietic malignancy in dogs, and relapse is frequently seen despite aggressive initial treatment. In order for the treatment of these recurrent lymphomas in dogs to be effective, it is important to choose a personalized and sensitive anticancer agent. To provide a reliable tool for drug development and for personalized cancer therapy, it is critical to maintain key characteristics of the original tumor. Objectives: In this study, we established a model of hybrid tumor/stromal spheroids and investigated the association between canine lymphoma cell line (GL-1) and canine lymph node (LN)-derived stromal cells (SCs). Methods: A hybrid spheroid model consisting of GL-1 cells and LN-derived SC was created using ultra low attachment plate. The relationship between SCs and tumor cells (TCs) was investigated using a coculture system. Results: TCs cocultured with SCs were found to have significantly upregulated multidrug resistance genes, such as P-qp, MRP1, and BCRP, compared with TC monocultures. Additionally, it was revealed that coculture with SCs reduced doxorubicin-induced apoptosis and G2/M cell cycle arrest of GL-1 cells. Conclusions: SCs upregulated multidrug resistance genes in TCs and influenced apoptosis and the cell cycle of TCs in the presence of anticancer drugs. This study revealed that understanding the interaction between the tumor microenvironment and TCs is essential in designing experimental approaches to personalized medicine and to predict the effect of drugs.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.249-256
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• 2013

How Th2 immunity develops in vivo remains obscure. Basophils have been considered key innate cells producing IL-4, a cytokine essential for Th2 immunity. Increasing evidence suggests that basophils are dispensable for the initiation of Th2 immunity. In this study, we revisited the role of basophils in Th2 immune responses induced by various types of adjuvants. Mice deficient in IL-3 or IL-3 receptor, in which basophil lymph node recruitment is completely abolished, fully developed wild type level Th2 CD4 T cell responses in response to parasite antigen or papain immunization. Similar finding was also observed in mice where basophils are inducibly ablated. Interestingly, IL-4-derived from non-T cells appeared to be critical for the generation of IL-4-producing CD4 T cells. Other Th2 promoting factors including IL-25 and thymic stromal lymphopoietin (TSLP) were dispensable. Therefore, our results suggest that IL-3- and basophil-independent in vivo Th2 immunity develops with the help of non-T cell-derived IL-4, offering an additional mechanism by which Th2 type immune responses arise in vivo.

• Journal of Life Science
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• v.34 no.5
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• pp.356-364
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• 2024

Lymph nodes (LNs) are crucial sites where immune responses are initiated to combat invading pathogens in the body. LNs are organized into distinctive compartments by stromal cells. Stromal cell subsets constitute special niches supporting the trafficking, activation, differentiation, and crosstalk of immune cells in LNs. Fibroblastic reticular cells (FRC) are a type of stromal cell that form the three-dimensional structure networks of the T cell-rich zones in LNs, providing guidance paths for immigrating T lymphocytes. FRCs imprint immune responses by supporting LN architecture, recruiting immune cells, coordinating immune cell crosstalk, and presenting antigens. During inflammation, FRCs exert both spatial and molecular regulation on immune cells through their topological and secretory responses, thereby steering immune responses. Here, we propose a model in which FRCs regulate immune responses through a three-part scheme: setting up, supporting, or suppressing immune responses. FRCs engage in bidirectional interactions that enhance T cell biological efficiency. In addition, FRCs have profound effects on the innate immune response through phagocytosis. Thus, FRCs in LNs act as gatekeepers of immune responses. Overall, this study aims to highlight the emerging roles of FRCs in controlling both innate and adaptive immunity. This collaborative feedback loop mediated by FRCs may help maintain tissue function during inflammatory responses.

• Journal of Life Science
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• v.26 no.9
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• pp.1027-1032
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• 2016

Antigen is substance causing disease derived from pathogen. Living organism has the immune system in terms of defense mechanism against antigen. Antigen is processed through several pathways such as phagocytosis, antibody action, complement activation, and cytotoxins by NK or cytotoxic T lymphocyte via MHC molecule. Lymph node (LN) is comprised of the complicated 3 dimensional network and several stromal cells. Fibroblastic reticular cells (FRC) are distributed in T zone for interaction with T cells. FRC produces the extra cellular matrix (ECM) into LN for ECM reorganization against pathogen infections and secretes homing chemokines. However, it has not so much been known about the involvement of the antigen process of FRC. The present report is for the function of FRC on antigen process. For this, FRC was positioned with several infected situations such as co-culture with macrophage, T cell, lipopolysaccharide (LPS) and TNFα stimulation. When co-culture between FRC with macrophage and T cells was performed, morphological change of FRC was observed and empty space between FRCs was made by morphological change. The matrix metallo-proteinase (MMP) activity was up-regulated by Y27632 and T cells onto FRC. Furthermore, inflammatory cytokine, TNFα regulated the expression of adhesion molecules and MHC I antigen transporter in FRC by gene chip assay. NO production was elevated by FRC monolayer co-cultured with macrophage stimulated by LPS. GFP antigen was up-taken by macrophage co-cultured with FRC. Collectively, it suggests that FRC assists of the facilitation of antigen process and LN stroma is implicated into antigen process pathway.

• Journal of Pathology and Translational Medicine
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• v.52 no.6
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• pp.369-377
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• 2018

Background: Chemokine receptor CXC chemokine receptor type 4 (CXCR4) and its ligand CXC motif chemokine 12 (CXCL12; stromal cell-derived factor-1) are implicated in tumor growth, metastasis, and tumor cell-microenvironment interaction. A number of studies have reported that increased CXCR4 expression is associated with worse prognosis in triple-negative breast cancer (TNBC), but its prognostic significance has not been studied in TNBC patients treated with adjuvant chemotherapy. Methods: Two hundred eighty-three TNBC patients who received adjuvant chemotherapy were retrospectively analyzed. Tissue microarray was constructed from formalin-fixed, paraffin-embedded tumor tissue and immunohistochemistry for CXCR4 and CXCL12 was performed. Expression of each marker was compared with clinicopathologic characteristics and outcome. Results: High cytoplasmic CXCR4 expression was associated with younger age (p=.008), higher histologic grade (p=.007) and lower pathologic stage (p=.045), while high CXCL12 expression was related to larger tumor size (p=.045), positive lymph node metastasis (p=.005), and higher pathologic stage (p=.017). The patients with high cytoplasmic CXCR4 experienced lower distant recurrence (p=.006) and better recurrence-free survival (RFS) (log-rank p=.020) after adjuvant chemotherapy. Cytoplasmic CXCR4 expression remained an independent factor of distant recurrence (p=.019) and RFS (p=.038) after multivariate analysis. Conclusions: High cytoplasmic CXCR4 expression was associated with lower distant recurrence and better RFS in TNBC patients treated with adjuvant chemotherapy. This is the first study to correlate high CXCR4 expression to better TNBC prognosis, and the underlying mechanism needs to be elucidated in further studies.