Enhanced Tumorigenicity, Melanogenesis, and Metastases of a Human Malignant Melanoma After Subdermal Implantation in Nude Mice

Abstract

Transplantation of human tumors into the organ or tissue of their origin (orthotopic transplantation) in nude mice can result in significant enhancement of tumor growth and metastases, compared with sc (ectopic) transplantation. Because melanocytes are normally found in the epidermal-dermal junction, intradermal inoculation of melanoma cells might be expected to improve their potential for malignant growth as xenografts. The purpose of our study was to examine this possibility. We found that because mouse epidermis and dermis are so thin, it was not possible to inject a bolus of tumor cells intradermally; instead the cells were actually deposited in the most superficial layer of the subcutis (i.e., subdermally). We evaluated the behavior of cells from a human melanoma cell line after sc or subdermal inoculation into National Institutes of Health Swiss athymic nude mice. The cells used were from (1) the predominantly amelanotic human malignant melanoma cell line MeWo, originally established from a melanotic lymph node metastasis, and (2) two MeWo variants resistant to wheat germ agglutinin (WGAr), which were selected for altered malignant capacities. Whereas 5 X 10(5) MeWo cells were required to achieve 100% tumor take with sc injection, only 2 x 10(4) cells were required with subdermal inoculation. Subdermal injection of the MeWo cells resulted in the development of highly melanotic and nonencapsulated primary tumors, which grew quickly into the dermis and epidermis and metastasized at high frequency to draining lymph nodes. In contrast, the tumors that developed after sc injection were found in the deepest layer of the subcutis and were predominantly amelanotic and encapsulated; they rarely metastasized to lymph nodes.(ABSTRACT TRUNCATED AT 250 WORDS)

‘Proteolytic switching’: opposite patterns of regulation of gelatinase B and its inhibitor TIMP-1 during human melanoma progression and consequences of gelatinase B overexpression

“…Fifty microlitres of cell suspension (1.0 ϫ 10 6 cells for WM 239 and WM 115); 2.0 ϫ 10 5 for WM 239/WM 239.92 or MeWo/ MeWo.92) was injected subdermally into the sides of each of four (WM 115 and WM 239) or five (WM 239/WM 239.92 or MeWo/MeWo.92) 6-to 8-week-old female nu/nu mice (Cornil et al, 1989). Tumour growth was monitored using calipers to measure two dimensions of the tumour and then applying the following formula to approximate tumour volume: volume (cm 3 ) ϭ width 2 ϫ (length/2).…”

Orthotopic human melanoma xenograft model systems for studies of tumour angiogenesis, pathophysiology, treatment sensitivity and metastatic pattern

“…Orthotopic inoculation seems to be particularly imxportant for accurate reproduction of the metastatic behaviour of human tumours (Fidler, 1991). Thus, intradermal inoculation of human melanoma cells in athymic mice resulted in primary tumours that metastasised at high frequency to draining lymph nodes, wlhreas the primary tumours that developed after subcutaneous inoculation of the same cells rarely gave rise to lymph node meastases (Cornil et al, 1989 Cell line (2.5 ± 0.4) x 10-' (1.6 ± 0.7) x 10-' (2.2 ± 0.9) x 10-Xenograft (2.2±0.5)x 10' (l.9±0.9)x 10-' (2.8±0.7)x 10-' D-12 Patient's tumour (1.5 ± 0.4) x 10' (7.5 ± 0.9) x 10' (4.9 ± 1.0) x 10-2 Cell hne (1.3 ± 0.4) x 10-(7.4 ± 0.6) x 10-' (4.0± 1.2) x 10-2 Xenograft (1.7 ± 0.5) x 10-' (7.0± 0.8) x 10-' (4.4 ±0.9) x 10-2 R-18…”

Overexpression of normal and mutated forms of HRAS induces orthotopic bladder invasion in a human transitional cell carcinoma.

“…Such evidence is provided in this paper, and it derives from exploiting developments in orthotopic transplantation of human cancers in nude mice (17), in particular, bladder cancers (18). Such procedures often permit expression of invasive and/or metastatic spread that is otherwise not generally observed after conventional subcutaneous (ectopic) injection of human tumors in nude mice (17)(18)(19). Thus, Jones and colleagues (18) have reported that when cell lines established from invasive bladder cancers were injected transurethrally into nude mice, they retained an invasive phenotype and invaded through the mouse bladder wall in much the same manner as they do clinically.…”