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Carcinogenesis

Absence of the CD44 Gene Prevents Sarcoma Metastasis

Georg F. Weber, Roderick T. Bronson, John Ilagan, Harvey Cantor, Rudolf Schmits and Tak W. Mak
Georg F. Weber
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Roderick T. Bronson
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John Ilagan
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Harvey Cantor
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Rudolf Schmits
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Tak W. Mak
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DOI:  Published April 2002
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    Fig. 1.

    Tumor invasiveness. A–F, osteosarcomas in trp53+/tm1 mice and their metastases in lungs and liver. A, primary tumor in CD44+/+ background; B, representative lung metastasis in CD44+/+ background; C, representative liver metastasis in CD44+/+ background; D, primary tumor in CD44−/− background; E, only metastasis detected in CD44−/− background (H&E); F, incidence of metastases in livers and lungs from osteosarcoma bearing mice.

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    Fig. 2.

    Expression of CD44. A and B, immunohistochemistry for CD44 expression in osteosarcomas from a trp53+/tm1 CD44+/+ (A) and a trp53+/tm1 CD44−/− mouse (B). In C and D, typing of the mice was performed by flow cytometry with FITC-anti-CD44 on spleen cells and lymph node cells (data not shown) and by PCR on genomic DNA with published primers (11) ; C, CD44+/+; D, CD44−/−.

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    Fig. 3.

    Intestinal polyps caused by the min mutation of the APC gene are not invasive. Histology of representative intestinal polyps from APC+/min mice. The largest polyp from each intestine was sectioned in the middle and stained with H&E for histological assessment of signs for malignancy. Regardless of the presence of the CD44 gene, the basement membrane remains intact (arrows). A, CD44+/+; B, CD44−/−.

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    Fig. 4.

    Tumor incidence. The numbers of intestinal polyps were counted in APC+/min mice at the end of their life span (average 209 days for 10 APC+/minCD44+/+ mice and 236 days for 15 APC+/minCD44−/− mice). The incidence of spontaneous polyps was assessed at an average of 433 days for 3 APC+/+CD44+/+ mice and 437 days for 3 APC+/+CD44−/− mice. Symbols, individual data points; mean values are presented as horizontal lines.

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    Fig. 5.

    Carcinomas in mice with one mutant p53 allele. Histology of sporadic carcinomas in trp53+/tm1 mice, including a squamous cell carcinoma (CD44+/+; top) and a lung carcinoma (CD44−/−; bottom). The slides are stained with H&E.

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    Fig. 6.

    Kaplan-Meier survival curves. A, survival of APC+/min mice with wild-type (▪) or deleted (•) CD44 gene. All APC+/+ mice survived the 420-day period of observation. B, survival of trp53+/tm1 mice. Within 600 days, mice with the trp53+/tm1 genotype succumbed to various tumors independently of their CD44 status, leading to survival of 4% or 1 mouse (CD44+/+, ▵) and 23% or 6 mice (CD44−/−, ▪). Control mice with the wild-type trp53 gene had survival rates of 87% or 14 mice (CD44+/+, ▴) and 83% or 30 mice (CD44−/−, □).

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    Characterization of solid tumors in trp53+/tm1 mice. Incidence, associated life span, and tumor weight at the time of death are specified for each histologic type of sarcoma for CD44+/+ and CD44−/− genetic background. Life span and tumor weight are indicated as mean ± standard error.

    TumorIncidenceLife spanWeight
    Osteosarcoma
     trp53CD446 (25%) 5 f, 1 ma532 ± 30 daysP > 0.057.7 ± 2.4 gramsP > 0.05
     trp53CD444 (15%) 3 f, 1 m467 ± 56 days6.1 ± 1.7 grams
    Fibrosarcoma
     trp53CD447 (29%) 4 f, 3 m410 ± 23 daysP > 0.0521.9 ± 5.0 gramsP > 0.05
     trp53CD447 (27%) 5 f, 2 m403 ± 30 days12.3 ± 2.9 grams
    Hemangiosarcoma
     trp53CD443 (12%) 2 f, 1 m304 ± 51 days10.7 ± 8.1 grams
     trp53CD440 (0%)
     trp53CD441 (3%) 1 m595 days2.9 grams
    Histiocytic sarcoma
     trp53CD442 (8%) 2 m589/590 days
     trp53CD441 (4%) 1 f420 days
     trp53CD441 (6%) 1 m600 days
    • a f = female; m = male.

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Cancer Research: 62 (8)
April 2002
Volume 62, Issue 8
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Absence of the CD44 Gene Prevents Sarcoma Metastasis
Georg F. Weber, Roderick T. Bronson, John Ilagan, Harvey Cantor, Rudolf Schmits and Tak W. Mak
Cancer Res April 15 2002 (62) (8) 2281-2286;

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Absence of the CD44 Gene Prevents Sarcoma Metastasis
Georg F. Weber, Roderick T. Bronson, John Ilagan, Harvey Cantor, Rudolf Schmits and Tak W. Mak
Cancer Res April 15 2002 (62) (8) 2281-2286;
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