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K Harigaya

Publications and source records attributed to K Harigaya.

At least 37 records · Page 2Linked to original sources
PubMed1996

Interleukin-6 inhibits the chemotaxis of human malignant plasma cell lines.

The chemotaxis of human malignant plasma cells is promoted by two extracellular matrix proteins (ECMs): fibronectin (FN) and laminin (LN). We examined the effect of the supernatant from a bone marrow stroma cell line, KM-101, on the chemotaxis of human malignant plasma cell lines to assess the chemotaxis-regulatory roles of the bone marrow microenvironment. Five human malignant plasma cell lines, FR4ds, OPM-1ds, U266/B1, RPMI-8226 and ARH-77 showed different profiles of the expression of beta 1 integrins of FN and LN receptors. FR4ds, OPM-1ds and U266/B1 cells showed chemotaxis promoted by FN (ChFN) and LN (ChLN). ARH-77 cells showed ChFN but not ChLN. RPMI-8226 cells did not show either ChFN or ChLN. The supernatant from KM-101 cells inhibited the chemotaxis of each of these cell lines regardless of whether the chemotaxis was promoted by FN or LN. Among the cytokines produced by KM-101 cells, it was postulated that IL-6 mediated this inhibitory effect because anti-IL-6 monoclonal antibody (MoAb) and anti-IL-6 receptor MoAb significantly reversed the inhibition. Recombinant IL-6 (rIL-6) also exhibited a similar inhibitory effect. Because anti-gp130 MoAb significantly reversed the chemotaxis inhibitory effect of rIL-6, the inhibitory signal is probably transduced via the signal transducing receptor component, gp130. The chemotaxis-regulatory effect is another previously unrecognized function of this pleiotropic cytokine, IL-6. High levels of IL-6 in the bone marrow microenvironment of patients with multiple myeloma appears to be favourable for the localization of myeloma cells there.

Antigens, CD↗
PubMed1996

Tretinoin induces bone marrow collagenous fibrosis in acute promyelocytic leukaemia: new adverse, but reversible effect.

In 11/13 acute promyelocytic leukaemia (APL) cases treated with tretinoin (RA) we observed RA-induced inaspirable collagenous fibrosis of the bone marrow. To study the mechanism of RA on collagen production, we cultured a human bone marrow derived stromal cell line and an osteoblastic cell line with RA in vitro. 10(-7) and 10(-6)M of RA stimulated collagen production. Clinical and experimental observation may be important to understand this adverse effect of RA as it is useful in cancer chemoprevention as well as treatment for APL. This adverse effect is spontaneously reversible after stopping RA or following chemotherapy.

Adult↗
PubMed1995

[Expression of CD44 metastatic variant mRNA in colorectal carcinomas and its role in tumor metastasis and invasion].

The expression of CD44 molecules was investigated in colorectal carcinomas by RT-PCR and Southern Blot Analysis. There were significant differences between neoplastic and non-neoplastic colonic mucosa in the expression of CD44 metastatic variant mRNA. The CD44 metastatic variant mRNA was found to be increased in the neoplastic mucosa. However, we could not find metastasis-specific transcript in primary colorectal carcinomas. Our study suggests that the neoplastic transformation of colonic mucosa increases the expression of CD44 molecules, including the variant forms, which modulate the behavior of the tumor cells. The measurement of serum CD44 is useful in the estimation of tumor mass and its regression by treatment. Further investigation is needed to clearly understand the role of CD44 molecules in tumor metastasis and invasion.

Colorectal Neoplasms↗
PubMed1995

VLA-4-dependent adhesion in follicular non-Hodgkin's lymphomas.

The cellular contact between B cells and follicular dendritic cells (FDCs) in the germinal center is thought to play a key role in B-cell maturation and proliferation. The adhesion pathway through the very late antigen 4 (VLA-4) on the B cells and the vascular cell adhesion molecule 1 (VCAM-1) on the FDCs support this binding process. The neoplastic follicular centers in follicular non-Hodgkin's lymphomas (FNHLs) have similar structures and cellular components to those of normal germinal centers, but their interaction between B cells and FDCs may be functionally disturbed. In view of this we analyzed the interaction between VLA-4 and VCAM-1 molecules in the germinal center microenvironment, both in neoplastic and normal follicles. The structural characterization of FNHLs and reactive lymph nodes was studied with indirect immunohistochemical stainings using monoclonal antibodies against VLA-4, VCAM-1, and fibronectin, with special reference to the reaction pattern in the normal and neoplastic follicles. In the reactive follicular centers most B cells did not show a positive reaction for VLA-4, except for moderate reaction products in the B cells of the light zone. In FNHLs, on the other hand, most follicular center B cells were positive for VLA-4. The reaction patterns of VCAM-1 and fibronectin in both normal and neoplastic follicular centers were not basically different. To investigate the interaction of VLA-4 with VCAM-1 in both neoplastic and normal follicular centers, we performed a frozen-section binding assay, which found decreased binding between VLA-4 and VCAM-1 in FNHLs. The results of this study indicated that the microenvironment in neoplastic follicular centers is different from that in their normal counterparts, in terms of the characteristic distribution pattern of the VLA-4-positive B cells, and the functional deterioration of the VCAM-1 on FDCs.

Cell Adhesion↗
PubMed1994

Retinoids (all-trans and 9-cis retinoic acid) stimulate production of macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor by human bone marrow stromal cells.

Retinoic acids (RAs) exert pleiotropic effects on cellular growth and differentiation. All-trans retinoic acid (ATRA) and 9-cis retinoic acid (9-cis RA), a stereoisomer of ATRA, induce differentiation of leukemic cell lines and cells from patients with acute myelogenous leukemia (AML) in vitro. Despite information on the effects of RAs on hematopoietic cells, little is known about how RAs act on the hematopoietic microenvironment, especially on bone marrow stromal cells. Based on recent observations that various cytokines produced mainly by bone marrow stromal cells regulate hematopoiesis, we analyzed the effects of RAs on cytokine production by these cells. ATRA or 9-cis RA treatment of human bone marrow stromal cell line KM101, which produces macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) constitutively, enhanced mRNA levels of both cytokines in a dose-dependent manner. Both RAs also stimulated M-CSF production from primary cultures of human bone marrow stromal cells. Both retinoic acid receptor (RAR)-alpha and retinoid X receptor (RXR)-alpha were expressed constitutively in KM101 cells. ATRA did not affect the expression of either receptor, whereas 9-cis RA increased RXR-alpha mRNA expression in a dose-dependent manner, but did not affect levels of RAR-alpha mRNA. These findings may have important biologic implications for both the role of RAs in hematopoiesis and the therapeutic effects of ATRA on the hematopoietic microenvironment in patients with acute promyelocytic leukemia (APL).

Bone Marrow Cells↗
PubMed1994

Quantitative analysis of the two macrophage colony-stimulating factor mRNA expressed in a human stromal cell line by reverse transcription-polymerase chain reaction (RT-PCR).

We established a quantitative analysis system for 4.0 kb and 1.6 kb macrophage colony-stimulating factor (M-CSF) mRNA, using reverse transcription-polymerase chain reaction. Using this system, we performed quantitative analysis of the two mRNAs expressed in the human stromal cell line, KM102, in the resting condition and when stimulated by various concentrations of interferon-gamma (IFN-gamma). The expression of 1.6 kb M-CSF mRNA was more efficiently stimulated by IFN-gamma than that of 4.0 kb M-CSF mRNA. The alternative splicing of a single M-CSF gene has been shown to generate several M-CSF proteins with different localization; we believe that molecular analysis of the transcription products by this system is important to better understand the physiological significance of the different species of M-CSF derived from each mRNA.

Base Sequence↗
PubMed1994

Production of human granulocyte colony stimulating factor by various kinds of stromal cells in vitro detected by enzyme immunoassay and in situ hybridization.

Production of human granulocyte colony stimulating factor (G-CSF) by stromal cells was studied in vitro. Induction of G-CSF by interleukin 1 (IL-1) and lipopolysaccharide (LPS) was compared using enzyme immunoassay in various kinds of stromal cells. Primary human bone marrow stromal cells, a human bone marrow-derived stromal cell line (KM-102), and peripheral blood monocytes secreted small amounts of G-CSF without stimulation, while vascular endothelial cells and skin fibroblasts secreted G-CSF only when induced by IL-1 or LPS. The production of G-CSF by monocytes was stimulated predominantly by LPS, whereas that by KM-102 cells, endothelial cells, and fibroblasts was induced by IL-1 but much less so by LPS. IL-1 and LPS stimulated similar levels of G-CSF production by primary bone marrow stromal cells which consisted of various types of cells. In situ hybridization for G-CSF mRNA showed that only a small proportion of primary bone marrow stromal cells expressed a large amount of G-CSF mRNA upon stimulation. The positive cells were round or oval in shape, while most of the spindle-shaped stromal cells were negative for specific grains. Although further characterization of positive cells is needed, the results suggest that bone marrow stromal cells are heterogeneous in terms of their capacity for G-CSF production.

3T3 Cells↗
PubMed1994

Establishment of a human thymic stromal cell line (R-3-4) and its adhesive capacity with T cells in vitro.

T cells are considered to be activated in the thymus, and it has been emphasized recently that the thymic stromal cells play an important role in the process of T-cell maturation. To clarify how the stromal cells interact with T cells a cloned stromal cell line from human thymus was established and its adhesive capacity with T cells was studied. A recombinant plasmid, pSV3gpt containing SV40 large T antigen was introduced to human thymic stroma by the calcium phosphate co-precipitation method, and the thymic stromal cell line R-3-4 was obtained. Immunohistochemical examination showed that R-3-4 possessed with HLA-class 1 antigen, laminin, fibronectin, and keratin. To determine if the R-3-4 interacts with T cells, the binding activity of R-3-4 with T cells examined by using rosette formation technique. The R-3-4 formed rosette only with the T cells, but both B cells and myeloid cells did not bind to the R-3-4. This rosette formation between R-3-4 and T cells was inhibited when T cells were pretreated with anti-CD2 antibodies, suggesting that some mechanism involving CD2 participates in this binding. Our novel established thymic stromal cell line might be useful for studying the interactions between thymic stroma and T cells in vitro.

Antibodies, Monoclonal↗
PubMed1994

[Peripheral T cell lymphoma (immunoblastic type, HTLV-1 negative) associated with aganglionosis of the intestine].

A 56-year-old female was hospitalized in 1992, because of fever and lymphadenopathy. She had ileus due to aganglionosis of the intestine diagnosed in 1990. Blood tests disclosed anemia and thrombocytopenia. Peripheral blood smear demonstrated 69.5% abnormal cells and a T-cell origin was demonstrated on cell marker study by flow cytometry. Immunological examinations, including serum HTLV-1 antibody were negative. Lymph node biopsy revealed malignant lymphoma; diffuse large, immunoblastic. The clonality of the T-cell malignancy was shown by detecting rearrangement of T-cell receptor beta gene. A diagnosis of PTCL, high grade, immunoblastic, was made. The patient received various chemotherapeutic agents and achieved a short remission, then died 5 months after the diagnosis. The classification of T-cell lymphoma was established by Suchi and the Kiel classification. Many ATL/L cases have been reported in Japan before the above classification was affirmed, although there have been few reports of ATL/L-like diseases in which serum HTLV-1 antibodies were negative. The case reported here was HTLV-1 negative, although the patient was diagnosed as ATL/L-like disease, because the results of various laboratory examinations were similar to these of HTLV-1 positive cases. Characteristics of this case included a female patient and leukemic clinical features, because the gender preponderance of PTCL, high grade, immunoblastic is male and the clinical features of the disease are not usually leukemic. It was also characteristic that PTCL coexisted with aganglionosis of the intestine. Basic disturbances in the latter condition would be similar to aganglionic megacolon in which a possible aberrant immune mechanism was shown.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1994

Alteration of the proteoglycan form of macrophage colony-stimulating factor produced by a human stromal line stimulated by tumor necrosis factor-alpha.

Immunoblot analysis of macrophage colony-stimulating factor (M-CSF) in KM 102 cell-conditioned medium showed the presence of two M-CSF molecular types, one being 85-kd M-CSF, the other a proteoglycan form (PG-M-CSF) carrying a chondroitin sulfate chain of variable length. When KM 102 cells were stimulated by TNF-alpha, they produced more M-CSF than that produced in unstimulated condition, in which PG-M-CSF had a shorter chondroitin sulfate chain. Although PG-M-CSF has binding affinity for type V collagen, the PG-M-CSF with the shorter chondroitin sulfate chain shows lower affinity. This spreads in type V collagen-containing agarose gel more easily than does PG-M-CSF with a longer chondroitin sulfate chain.

Bone Marrow Cells↗
PubMed1993

Binding of membrane-anchored macrophage colony-stimulating factor (M-CSF) to its receptor mediates specific adhesion between stromal cells and M-CSF receptor-bearing hematopoietic cells.

To explore the biologic significance of the membrane-anchored form of macrophage colony-stimulating factor (M-CSF), we examined whether interaction between membrane-bound M-CSF and its receptor mediates intercellular adhesion as well as cell proliferation and differentiation. Human M-CSF receptors were expressed on a murine interleukin-2 (IL-3)-dependent cell line, FDC-P2, by DNA transfection with the c-fms gene (FDC-P2-MCSFR). A human bone marrow-derived stromal cell line, KM102, was used in the cell adhesion assay. The expression of membrane-bound M-CSF on KM102 cells was demonstrated by flow cytometry and immunoblot analysis. After the incubation of parent and transformed FDC-P2 cells on confluent KM102 cells, nonadherent cells were removed and the cells attached to KM102 cells were examined microscopically. Almost all parent FDC-P2 cells were nonadherent, whereas a significant number of FDC-P2-MCSFR cells bound to KM102 cells. The addition of anti-M-CSF or anti-M-CSF receptor neutralizing antibodies dose-dependently inhibited the binding of [3H]-thymidine-labeled FDC-P2-MCSFR cells to KM102 cells. An excess amount of M-CSF also inhibited the binding. On the other hand, the addition of antibodies against some representative adhesion molecules (vitronectin receptor, Pgp-1/CD44, and VLA-4) did not inhibit the adhesion between FDC-P2-MCSFR cells and KM102 cells. These results support the idea that membrane-anchored M-CSF and its receptor may function as mediators of cell-cell adhesion.

Animals↗