TY - JOUR
T1 - Demonstration of multiple phenotypic diversity in a murine melanoma of recent origin1, 2, 3, 4
AU - Barnes, Zoa
AU - Fidler, Isaiah J.
AU - Gruys, Eilene
AU - Cifone, Maria A.
AU - Bucana, Corazon
N1 - Funding Information:
I Received February 17. 1981; accepted May 29. 1981. 2 Supported by Public Health Service contract NOI-C075380 from the Office of the Director. National Cancer Institute. with Litton Bionetics. Inc. J The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Health and Human Services nor does mention of tradenames. commercial products. or organizations imply endorsement by the U.S. Government. 4 Animals were maintained under the guidelines set forth by the National Institutes of Health Policy on Humane Care and Use of Animals and by the Animal Welfare Act in facilities accredited by the American Association for Accreditation of Laboratory Animal Care. l Cancer Metastasis and Treatment Laboratory, NCI Frederick Cancer Research Center. P.O. Box B. Frederick, Md. 21701. 6 Cancer Biology Program. NCI Frederick Cancer Research Center. 7 We thank Ms. Diane Plentovich for her technical assistance and Mr. Charles Riggs for statistical analysis of the data.
PY - 1981/10
Y1 - 1981/10
N2 - The purpose of these studies was to examine whether the metastatic heterogeneity that is frequently found in serially transplanted neoplasms could be observed in a murine melanoma of recent origin. The primary K-1735 melanoma that arose in an inbred C3H/HeN murine mammary tumor virusnegative (C3Ha) mouse was transplanted once into an immunosuppressed recipient and then established in culture. Cells from the fifth in vitro passage were used to produce clones. The parent K-1735 and 22 cloned lines were tumorigenic in syngeneic and outbred N:NIH(S) nude mice. Metastatic properties were assessed by observing the ability of the cells to produce pulmonary and extrapulmonary lesions after they were injected iv into 6-week-old C3Ha mice. The number of metastases produced, their relative size, and pigmentation varied dramatically among the clones. Only 2 of 22 clones were indistinguishable from the parent tumor. Most of the nonmetastatic (but tumorigenic clones) were also nonmetastatic in 3-week-old nude mice, which suggests that the absence of metastasis formation was not merely due to their immunologic rejection by the normal C3Ha mouse. Control subcloning experiments demonstrated that the procedure of cloning in vitro was not responsible for the variability among the clones. The clones did not differ in their karyotype or cell size, but they did differ in their growth rate in vitro. These phenotypes, however, did not correlate with metastatic propensity. In conclusion, the K-1735, a murine melanoma of most recent origin, is heterogeneous and contains subpopulations of cells with diverse biologic behavior.
AB - The purpose of these studies was to examine whether the metastatic heterogeneity that is frequently found in serially transplanted neoplasms could be observed in a murine melanoma of recent origin. The primary K-1735 melanoma that arose in an inbred C3H/HeN murine mammary tumor virusnegative (C3Ha) mouse was transplanted once into an immunosuppressed recipient and then established in culture. Cells from the fifth in vitro passage were used to produce clones. The parent K-1735 and 22 cloned lines were tumorigenic in syngeneic and outbred N:NIH(S) nude mice. Metastatic properties were assessed by observing the ability of the cells to produce pulmonary and extrapulmonary lesions after they were injected iv into 6-week-old C3Ha mice. The number of metastases produced, their relative size, and pigmentation varied dramatically among the clones. Only 2 of 22 clones were indistinguishable from the parent tumor. Most of the nonmetastatic (but tumorigenic clones) were also nonmetastatic in 3-week-old nude mice, which suggests that the absence of metastasis formation was not merely due to their immunologic rejection by the normal C3Ha mouse. Control subcloning experiments demonstrated that the procedure of cloning in vitro was not responsible for the variability among the clones. The clones did not differ in their karyotype or cell size, but they did differ in their growth rate in vitro. These phenotypes, however, did not correlate with metastatic propensity. In conclusion, the K-1735, a murine melanoma of most recent origin, is heterogeneous and contains subpopulations of cells with diverse biologic behavior.
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U2 - 10.1093/jnci/67.4.947
DO - 10.1093/jnci/67.4.947
M3 - Article
C2 - 6944560
AN - SCOPUS:0019787737
SN - 0027-8874
VL - 67
SP - 947
EP - 956
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
IS - 4
ER -