Comparison of metastatic cell lines derived from a murine mammary tumour, and reduction of metastasis by heparin

Abstract

A murine mammary carcinoma, which had a high potential for metastasis to the lungs, was established in culture, and from the parent line several clonally derived variants were isolated, showing different characteristics including metastatic potential. C1, a high metastatic clone, and C2, a low one, were selected for further study. When tumour cells were injected s.c. the growth rates of the resulting tumours were higher when they developed from the parent line (P2) or C1 cells, than from C2 cells. The numbers of lung colonies seen following i.v. inoculation of tumour cells also varied, C2 cells yielding the lowest score. In vitro C1 cells were more efficient at aggregating platelets than C2, an effect reduced by the addition of heparin. In vivo heparin reduced the number of tumour cells arrested in the lungs after i.v. injection, and also the number lung colonies which subsequently became established. The number of metastases which developed following s.c. injection of tumour cells was also reduced by heparin.

Antimetastatic activities of heparins and modified heparins. Experimental evidence

“…Intravenous application of heparin around the time of tumor cell injection always led to reduction of metastasis. Subcutaneous or intraperitoneal application of heparin around the time of tumor cell injection led mostly to attenuation of metastasis [11,14,20,[25][26][27], while in some studies the affectivity of heparin was limited [17,[28][29][30]. Attenuation of metastasis was repeatedly observed in most of the studies despite a wide range of heparin dosages applied (Table 1).…”

Prevention of Thrombothic Complications in Cancer Patients in High-Risk Groups

“…Гепарины способны оказывать антиангиогенное действие за счет торможения формирования ангиогенного матрикса (фибриновых структур) и предотвращения активации протеаз коагуля-ционного каскада (в первую очередь тромбина), способ-ствующего повышению продукции сосудистого эндотели-ального фактора роста (VEGF) [26]. Кроме того, гепарины, взаимодействуя с молекулами адгезии, способны тормо-зить метастазирование опухолей [27].…”

Thrombohemorrhagic events in cancer surgery

“…Использование НМГ у онкологических больных также предпо-чтительно в связи с наличием сведений об их влиянии на течение опухолевого процесса и улучшением прогноза выживаемости [20][21][22][23][24][25], хотя для этого утверждения необходимо проведение дальнейших исследований у пациентов с различными типами и стадиями заболевания.…”