Capacity For Autonomous Growth Research Articles

Diffuse-type giant cell tumor of the subcutaneous thigh

Diffuse-type giant cell tumor is an extra-articular form of pigmented villonodular synovitis. The localized form of this lesion (tenosynovial giant cell tumor) is frequent, representing the most common subset arising from the synovium of a joint, bursa or tendon sheath, with 85% of cases occurring in the fingers. The less frequent diffuse-type giant cell tumors are commonly located in the periarticular soft tissues, but on rare occasions these lesions can be purely intramuscular or subcutaneous We report the case of a 26-year-old female with diffuse-type giant cell tumor of the subcutaneous thigh, remote from a joint, bursa or tendon sheath. A review of the literature did not reveal any similar description of a diffuse-type giant cell tumor completely within the subcutaneous thigh, remote from a joint, bursa or tendon sheath. These lesions were initially regarded as inflammatory or reactive processes, but since the identification of clonal abnormalities in these patients, and in view of their capacity for autonomous growth, they are now widely considered to represent benign neoplasms.

Transplantation studies on induced and spontaneous nodules from B6C3F1 mouse liver.

The present research was designed to assess the potential for progressive growth of hyperplastic, adenomatous, and carcinomatous mouse liver lesions grafted into syngeneic hosts and to determine the effect of treatment type, donor age, and metastatic potential on this parameter. Lesions were obtained from male B6/C3F1 mice fed on an open formula (NIH-007) diet or the same diet mixed with a chlorinated hydrocarbon pesticide (3,5-dichloro-(N-1,1-dimethyl-2-propyl)benzamide) (DcB). Animals were killed at 18 or 24 months of age. Hosts for transplanting were killed at 8 months, or when grafts reached 2 cm in diameter. Lesions diagnosed as nonmalignant (hyperplastic or benign) were more likely to grow after transplantation if obtained after 24 months, rather than after 18 months (0.025 less than p less than 0.05). There was a close correlation between donor lesion morphology and ability to grow in a recipient mouse (p less than 0.0005; 36% of the hyperplastic, 32% of the adenomatous and 79%, of the malignant lesions grew). The majority of lesions retained the morphologic appearance of the donor lesions. Transplanted lesions from control mice were more likely to grow than were those from DCB-treated mice (0.01 less than p less than 0.025). This correlation was particularly strong for hyperplastic nodules. Metastatic capability in the donor animals correlated positively with both growth potential (p less than 0.01) and growth rate (p less than 0.05) in recipient mice. These findings suggest that progression toward autonomous growth may occur both within the original host and during a prolonged transplantation period, making data interpretation difficult. Lesion morphology alone may not be adequate for assessing capacity for autonomous growth. Other factors, such as evidence of metastasis or local invasion in the primary host, may be required to make more meaningful diagnosis.

Autogenous production of a hemopoietic growth factor, persisting-cell-stimulating factor, as a mechanism for transformation of bone marrow-derived cells.

Lines of hemopoietic progenitor cells can be grown for prolonged or indefinite periods in vitro in the presence of a specific growth factor produced by activated T lymphocytes, persisting (P)-cell-stimulating factor (PSF). From such a PSF-dependent line, we report the emergence of variants that had concomitantly acquired both the capacity for autonomous growth in the absence of exogenous PSF and the capacity for the autogenous production of PSF. The link between these two new properties was strengthened by the demonstration that the variant lines absorbed PSF and, in some culture conditions, responded to exogenous PSF. Thus when variant cells were plated at low density in 1-ml agar cultures, cloning efficiency and colony size were enhanced by supplementation with sources of PSF, including medium conditioned by concanavalin A-stimulated normal spleen cells, T-cell tumors and T-cell hybridomas, and, importantly, medium conditioned by the autonomous P-cell lines themselves. In contrast to the parental line, the autonomous clones tested formed progressively growing tumors in vivo. It is proposed that the myelomonocytic leukemia WEHI-3B that produces PSF arose from a neutrophil-macrophage progenitor through acquisition of the capacity for the autogenous production of PSF and that the autogenous production of PSF may play a similar role in a range of proliferative disorders both of the blood and of other tissues containing components derived from the bone marrow.

Suppression of the Tumorous State in Crown Gall Teratomas of Tobacco A Clonal Analysis

Two types of experimental approaches designed to test the possible involvement of chimeras in the persistent but readily reversible suppression of the tumorous state and in a recovery from that state in crown gall teratomas of tobacco were investigated. These studies showed that the tumorous state was suppressed in specialized cells present in the different tissues derived from each of the three layers of the apical meristem of teratoma-derived shoots of clonal origin. Although differences existed in the exogenous requirements needed for the reestablishment of the tumorous state in the different specialized cell types present in the different tissues, all again acquired a capacity for autonomous growth when appropriately stimulated. No evidence was found for the existence of periclinal or sectoral chimeras in teratoma-derived shoots of a single cell origin. Chimerism was, however, found to exist in one noncloned teratoma-derived shoot. Analysis of more than 500 clones derived from leaf mesophyll cells of cloned teratoma shoots showed that the vast majority of them (> 99%) were tumorous, while all of the 144 seed-grown plants from these shoots had completely recovered from the tumorous state. The results of these studies suggest that (a) a teratoma shoot does not depend for its development on the presence of significant numbers, if any, of cells that had recovered from the tumorous state; (b) the tumorous state may be suppressed in even the most highly specialized cells; (c) some special mechanism exists in the meiotic process for the elimination of all or most of the foreign DNA from transformed cells.

Genetic and biochemical studies on the suppression of and a recovery from the tumorous state in higher plants.

Four neoplastic diseases of plants: crown gall, which is caused by Ti plasmid DNA; Black's wound tumor disease by an RNA virus; the Kostoff genetic tumors by chromosomal imbalance; and habituation, which results from a spontaneous activation of select biosynthetic systems, have been analyzed and compared. It has been found that both the development of a capacity for autonomous growth and the nature of the heritable cellular change that underlies tumorigenesis are similar in the four instances. All develop a capacity for autonomous growth as a result of the persistent activation of select biosynthetic systems, the products of which are concerned with cell growth and division. That the persistent activation of these biosynthetic systems does not involve heritable changes of an irreversible type is indicated by the finding that a reversal of the neoplastic state occurred in three of the test systems. Since the tumor cells in these instances were found to remain totipotent the results suggest that whether the normal or tumor phenotype is expressed is determined by how the genetic information is regulated in a cell. Regulation appears to be accomplished in part through positive feedback control mechanisms. Foreign genetic information could act either in a regulatory manner to persistently activate normal biosynthetic systems or it could code for one or more essential but normally limiting substance(s) and thus replace a substance(s) that in the case of the Kostoff tumors or habituation is specified by host cell genes, or it could do both. In either case, the foreign genetic information can be regulated in much the same manner as are the host cell genes to give rise to either the normal or tumor phenotype.

Differential Expression of Oncogenicity and Nopaline Synthesis in Intact Leaves Derived from Crown Gall Teratomas of Tobacco

The results reported in the present study demonstrate that oncogenicity and nopaline synthesis are differentially expressed under conditions in which the neoplastic state is persistently suppressed in crown gall teratoma tissues of tobacco. While an active and continued synthesis of nopaline occurs in cells present in intact teratoma-derived leaves, the reexpression of oncogenicity depends on the development of new cell divisions. It is suggested that these new cell divisions are required either (a) to reestablish positive feedback control mechanisms upon which the development of a capacity for autonomous growth of these plant tumour tissues appears to depend, or (b) to establish the pattern of metabolism concerned with cell growth and division which is then maintained in the plant tumour cells by positive feedback control mechanisms.

The development of a capacity for autonomous growth of the crown gall tumor cell.

The development of a capacity for autonomous growth of the crown gall tumor cell.

A Study on the Nature of Autonomy in Neoplastic Plant Cells

lem of the growth of altered cells by more or less random division. The tumor cell is not, however, characterized primarily by its rate of growth since certain normal cell types may grow and divide at considerably faster rates than do most tumor cells. The tumor cell need not, moreover, be limited in a capacity to differentiate and functionate. Pluripotent teratoma cells possessing malignant properties are quite capable of showing a high degree of differentiation. The one biological character that distinguishes tumor cells from normal cells is the capacity for the uncontrolled or autonomous growth of the tumor cell within an organism. Without this there would be no tumors. Autonomy of neoplastic growth has many gradations. At the one extreme are the so-called benign tumors which commonly grow slowly and remain localized in the host. At the other extreme are the most malignant cancers which invade neighboring tissue and spread throughout an organism by metastasis. The nature of autonomy remains one of the foremost problems in cancer research. Since the capacity for autonomous growth is potentially a property of the cell itself, it should be equally capable of expression in the cells of all higher organisms whether they are of animal or plant origin. It does not necessarily follow, however, that the cellular mechanism, in terms of specific chemical reactions, is identical in members of the two kingdoms. The fundamental similarity of cells and cellular processes is, nevertheless, commonly recognized and advances in one field of investigation may assist in clarifying problems in related fields of study.