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F R Miller

Publications and source records attributed to F R Miller.

At least 91 records · Page 5Linked to original sources
PubMed1983

Tumor subpopulation interactions in metastasis.

Subpopulations isolated from a single mouse mammary tumor differ in ability to metastasize when tested independently in normal, syngeneic mice. The presence of a metastatic subpopulation, however, enabled relatively nonmetastatic subpopulations to metastasize. Tumor subpopulation 67 did not form metastatic nodules after intravenous injection of 3 X 10(6) cells. If injected with 1 X 10(4) cells of the metastatic subpopulation 410.4, colony-forming tumor 67 cells, as well as 410.4 cells, were found in the resulting lung nodules. Mice bearing subcutaneous implants of subpopulation 168 tumors and which were injected intravenously with saline or 1 X 10(4) of subpopulation 168 cells did not develop metastases. The intravenous injection of 1 X 10(4) of subpopulation 410.4 cells into mice bearing subcutaneously subpopulation 168 tumors resulted in lung nodules consisting of colony-forming 168 as well as 410.4 cells. Thus, the simultaneous presence of metastatic and nonmetastatic subpopulations can result in metastatic nodules containing the nonmetastatic subpopulation.

Animals↗
PubMed1983

Quantitative selectivity of contact-mediated intercellular communication in a metastatic mouse mammary tumor line.

We have examined contact-mediated intercellular communication by measuring the transfer of thioguanine sensitivity to a hypoxanthine phosphoribosyltransferase (EC 2.4.2.8)-negative clone (66cl-4) selected from one subline isolated previously from a spontaneously arising mammary tumor of a BALB/cfC3H mouse. We tested other sublines from the same tumor and unrelated cell types for their ability to serve as 6-thioguanine nucleotide donors to 66cl-4 cells. The degree of communication, measured by the number of donor cells required to reduce the number of thioguanine-resistant colonies, varied with the donor cell type. The 66cl-4 line communicated with the parent cell line from which the thioguanine-resistant cell was selected and with other sublines from the parent tumor, with some unrelated tumor cells, and with some nonneoplastic cells (3T3, hamster kidney and lung fibroblasts, and mouse mammary epithelial cells). There was a quantitative difference in the amount of communication which took place with the various cells tested, but no pattern of difference could be discerned. Line 66cl-4 did not preferentially communicate with cells of epithelial versus fibroblast morphology, nor with tumor versus nontumor cells. The 66cl-4 cells retained the ability of their parent line to form metastatic tumors when injected s.c. into BALB/c mice. A quantitative selectivity of communication is thus expressed in these malignant metastatic cells, but it is apparently unrelated to either the morphological or malignant phenotype of the donor. Contact-mediated communication between tumor subpopulations may differentially affect growth and drug sensitivity within a tumor.

Animals↗
PubMed1982

Intratumor immunologic heterogeneity.

Tumor cells express a great variety of antigens including tumor specific transplantation antigens, tumor-associated antigens, differentiation antigens, histocompatibility antigens, lectin-binding sites and receptors for natural killer cells and natural antibodies. These antigens are distributed unevenly on tumor subpopulations and each subpopulation may induce different immune responses to the same determinant. Intratumor immunologic heterogeneity arises early in cancer, possibly during preneoplasia, and exists throughout the course of progression. Metastatic subpopulations are not generally less antigenic than subpopulations within primary tumors. Different arrays of antigenic determinants are displayed by subpopulations but variability in cell surface expression of a single determinant is also a fundamental type of immunologic heterogeneity. Antigenic specificity patterns commonly reveal one-way cross-reactions between tumor subpopulations. One-way cross-reactions might occur due to quantitative differences, cell-cycle variations, modulation, masking, H-2 expression and restriction phenomena, or alteration in the carbohydrate side-chains of glycoproteins. Interactions which occur when subpopulations co-exist may alter immune responses so that the response to the mixture is not the sum of the responses to the individual subpopulations. It is suggested that the exploitation of the mechanisms involved in immunologic heterogeneity may lead to new therapeutic approaches and that the great diversity of determinants expressed by tumor cells could lead to development of multivalent panel of monoclonal antisera which, acting synergistically, could preferentially lyse tumor cells.

Animals↗
PubMed1981

Comparison of metastasis of mammary tumors growing in the mammary fatpad versus the subcutis.

The frequency with which metastasis occurs for three tumor sublines derived from a single mouse mammary tumor, all of which grow preferentially in mammary fatpads (as compared to the subcutis), was determined from primary tumors growing in mammary fatpads and from primary tumors growing in the subcutis. A relatively metastatic subline was found to metastasize more readily from the mammary fatpad than from subcutaneous sites. The number of metastatic nodules found in the lungs of animals following surgical removal of primary tumors transplanted into intact mammary fatpads was significantly greater than the number of nodules in the lungs of animals following surgical removal of primary tumors transplanted subcutaneously. Two sublines, which do not readily metastasize from tumors growing subcutaneously, did not metastasize from tumors growing in mammary fatpads.

Adipose Tissue↗
PubMed1981

Preferential growth of mammary tumors in intact mammary fatpads.

Four transplantable tumors, three (66, 410, and 168cl) isolated from a spontaneously occurring strain BALB/cfC3H mammary tumor and one (D2) arising from a BALB/c hyperplastic alveolar nodule were found to grow better in mammary fatpads than at s.c. sites. Furthermore, tumor growth was better (p less than 0.05) in intact mammary glands than in cleared mammary fatpads for the D2, 410, and 66 tumors (168cl was not tested). The role of immunity in these differences was investigated using the highly immunogenic 410 tumors. Tumor 410 induced equally effective immunity to subsequent challenge whether it was implanted s.c. or in intact fatpads. Furthermore, in immunized animals, Tumor 410 was rejected equally well when the challenge site was intact fatpad as when s.c. Similarly, Tumor 410 induced immunity after implantation into cleared fatpads and, in immunized animals, was rejected when the challenge site was the cleared fatpad. We thus found no evidence that the mammary fatpad is immunologically privileged, as compared to the s.c. site, with respect to tumor transplantation antigens.

Adipose Tissue↗
PubMed1980

Activity of lymphoid cells separated from mammary tumors in blastogenesis and Winn assays.

Lymphoid cells isolated from mouse mammary tumors by isokinetic gradients were not stimulated in vitro by either phytohemagglutinin or a soluble, tumor-associated antigen extract even though splenocytes from the tumor-bearing mice were responsive to both. In in vivo Winn assays, lymphoid cells isolated from tumors markedly stimulated tumor growth rate. The effect on growth rate was abrogated by exposure of the isolated lymphoid cells to antilymphocyte serum and complement.

Animals↗
PubMed1980

Growth interaction in vivo between tumor subpopulations derived from a single mouse mammary tumor.

Our laboratory has previously isolated several tumor cell populations from a single, spontaneously arising mammary tumor of a BALB/cfC3H mouse and established them in tissue culture as independent sublines. These subpopulations differ according to many criteria including growth parameters and expression of tumor-associated antigens. We have tested the interaction in vivo of several of these subpopulations by injecting cell suspensions of the same or different sublines into opposite flanks of BALB/cfC3H or BALB/c mice. The growth characteristics of certain subpopulations were altered by the presence of a different subpopulation on the opposite side. In order to understand the mechanism of interaction, we chose two subpopulations (410 and 168) for further study. In BALB/cfC3H mice, the presence of line 410 tumors on one flank inhibited both 410 and 168 tumors on the other flank. Line 168 tumors did not inhibit either 410 or 168 tumors. The inhibitory effect of line 410 appeared to be immunological, since (a) it was increased by injecting line 410 several weeks before line 168, (b) it was abrogated in mice subjected to 400-rad X-irradiation 2 days prior to tumor cell injection, (c) mice could be made resistant to both line 410 and line 168 tumors by implantation followed by surgical removal of line 410 but not of line 168, and (d) resistance could be adaptively transferred with lymph node cells from line 410-sensitized mice in Winn assays. Thus, immunity to tumor-associated antigens may be one way by which cells of a heterogeneous tumor can interact.

Animals↗
PubMed1979

Guinea pig cell-mediated tumor immunity: the chromium release assay detects both cytolysis and serum blocking for syngeneic chemically-induced tumors.

The chromium release test (CRT) was used to assess cell-mediated immunity to syngeneic, chemically-induced tumors in guinea pigs. The animal models were Sewall Wright strain 13 guinea pigs with 3-methyl-cholanthrene (MCA)-induced fibrosarcomas and strain 2 guinea pigs with diethylnitrosamine (DEN)-induced hepatocarcinomas. Regional lymph node cells were significantly cytolytic for the immunizing tumors, specifically so for three of the four tumors, and tumor-bearer sera could significantly block cytolysis. The two DEN-induced strain 2 hepatomas, line 1 and line 10, are antigenically distinct by the CRT but the two MCA-induced tumors have tumor specific antigens as well as a common, cross-reactive antigen.

Animals↗
PubMed1979

Cytolytic activity in vitro of lymph node cells after exposure in vivo to tumor cells suspended in blocking sera.

The in vivo effect of blocking sera (bs) on both tumor growth and subsequent in vitro cytolytic activity of regional lymph node cells was determined following injection of hepatoma cells suspended in normal sera (ns) or bs into the hind footpads of guinea pigs. Tumor growth was unaffected by bs but the primary response to tumor by LNC draining tumor/bs sites was significantly lower in 4/6 experiments as compared to cells from lymph nodes draining tumor/ns sites.

Animals↗
PubMed1979

Immunologic heterogeneity of tumor cell subpopulations from a single mouse mammary tumor.

Five subpopulations (66, 67, 68H, 168, and 4.10LM) obtained from a single BALB/cfC3H mammary adenocarcinoma were used to assess intratumor immunologic heterogeneity. BALB/c and BALB/cfC3H mice were immunized with each of the subpopulations, and lymph node cells (LNC) from immunized animals were tested for cell-mediated immunity (CMI) to each subpopulation in vitro by chromium release and microcytotoxicity tests and in vivo by Winn assays. The immunogenic character of the subpopulations differed markedly. The pattern of cross-reactivity indicated that at least two determinants were involved, one of which was probably a viral antigen. The viral antigen was expressed on 4 subpopulations (66, 68H, 168, and 4.10LM). The other determinant was immunogenic in both BALB/c and BALB/cfC3H mice and was expressed on 4 subpopulations (66, 67, 168, and 4.10lm). Thus 1 subpopulation (68H) expressed only the viral antigen, 1 (67) expressed only the other antigen, and 3 (66, 168, and 4.10LM) expressed both. Expression of the determinants showed qualitative and quantitative variations. Quantitative differences were noted by the relative effectiveness of the subpopulations to induce CMI and by the relative sensitivities to LNC-mediated killing. Qualitative differences were indicated by the occurrence of unidirectional cross-reactivities between some pairs of subpopulations; a determinant could be expressed so that the subpopulation could induce cytotoxic cells but not be sensitive to them or vice versa.

Adenocarcinoma↗
PubMed1979

Opposing effects of cryostat sections of preneoplastic and neoplastic mouse mammary lesions on in vitro migration of peritoneal exudate cells.

Cryostat sections of normal mouse tissues and of preneoplastic HAN and neoplastic mammary tumors were used as "antigens" in MMI tests. Nonspecific inhibition of normal and sensitized PEC migration was induced by HAN and some normal tissues, including normal mammary gland. This inhibition did not require the presence of lymphocytes, was not species specific, and could be blocked by sera from HAN-bearing mice. Cryostat sections of mammary tumors did not inhibit, indeed occasionally enhanced PEC migration. Further, the presence of tumor cryostats and eluates interfered with inhibition induced by HAN cryostats and by PPD with PEC from donors sensitized to that antigen. Histologic examination of HAN and of mammary tumor tissue revealed inflammatory cells to be distributed diffusely in the former and localized peripherally around the latter type of lesion.

Animals↗
PubMed1978

The importance of the ratio between effector and target cells for detection of serum blocking of tumor lymphocytolysis.

Sera from tumor-bearong guinea pigs were tested for their capacity to influence the magnitude of lymphocytolysis of tumor cells in vitro as measured by 51Cr release. Thirty-three sera were tested in 124 experiments in which the effector to target cell ratio (E:T) was 200:1. Significant blocking of cell-mediated lysis occurred in 62% of the experiments, whereas significant potentiation occurred in 7%. Six sera were found which showed significant blocking in some experiments and significant potentiation in other experiments. One of these sera was further evaluated by varying E:T, using lymphocytes from three immune donors. For each of the three populations of immune lymphocytes, significant blocking was demostrable only at one of three E:T tested. Blocking was observed only with an E:T of 200:1 in two cases. In a third case, blocking was observed at an E:T of 50:1, whereas an E:T of 200:1 gave rise to significant potentiation. The effect of these sera on lymphocytolysis in vitro is clearly dependent upon the E:T ratio.

Animals↗
PubMed1978

In situ lymphoid cells of mouse mammary tumors. III. In vitro stimulation of tumor cell survival by lymphoid cells separated from mammary tumors.

Lymphoid cells were isolated by isokinetic gradient centrifugation from mouse mammary tumors and evaluated for their ability to affect tumor cell survival with the microcytotoxicity assay. In all experiments stimulation of the growth or survival of tumor cells was seen. This stimulation was not seen with separated lymphoid cells treated with anti-lymphocyte serum and complement. The lymphoid cells separated from tumors were more stimulatory than were lymph node cells; even toxic to the tumor cells, the separated tumor-associated lymphoid cells were markedly stimulatory. The gradient procedure had no effect on the activity of sensitized lymph node cells, but it did separate cytotoxicity and stimulation into different fractions.

Animals↗
PubMed1978

Heterogeneity in drug sensitivity among tumor cell subpopulations of a single mammary tumor.

Three distinct subpopulations of tumor cells derived from a single parent strain BALB/cfC3H mammary adenocarcinoma were tested in vivo for sensitivity to cyclophosphamide, methotrexate, and 5-fluorouracil. Treatment was begun either 2 days after s.c. tumor cell injection or at the time when the tumors became palpable. It was given on a weekly basis for 4 weeks. The mice were observed for growth of the primary implant and for development of spontaneous metastases. The three subpopulations differed markedly in their sensitivity to the drugs. The effects of the drugs ranged from induction of regression of the "primary" to enhancement of metastases. The effect on primary growth was independent of that on metastasis. The effect of the time of administration of the drugs also varied among the subpopulations. The sublines were also tested in vitro with methotrexate and 5-fluorouracil. Again there were marked differences in sensitivity to inhibition of cell division by the drugs. The relative sensitivities in vitro did not correlate with observations in vivo. The existence of subpopulations of tumor cells, differing in sensitivity to therapeutic agents, within a single neoplasm, presents a challenge to development of assays capable of predicting drug response and to the selection of combination therapies.

Adenocarcinoma↗