Alternative site of implantation affects tumor malignancy and metastatic potential in mice: Its comparison to the flank model

Abstract

MC-C fibrosarcoma and B16F0 melanoma tumors were implanted intradermally in the dorsal region of the foot of mice. Tumor progression was compared to standard implantation in the flank. Although foot tumors only reached 13% (MC-C) and 25% (B16F0) of the mean volume of flank tumors, a more malignant phenotype in terms of histology and survival rate was observed in this type of tumors. Moreover, lung metastases were only detected in hosts bearing foot tumors, in contrast to MC-C and B16F0 populations with tumors growing in the flank. In addition, cellular influx and local immune reaction were higher in the dorsal region of the foot. According to our results, the dermis of the flank allows excessive tumor growth due to its low reactivity. Thus, differences in innate and adaptive immune effectors between the evaluated tumor microenvironments would account for the differences in tumor malignancy. Due to its striking differences with the standard flank inoculation, the tumor implantation model herein introduced could be a valuable tool to study the metastatic potential of different cell lines and the microenvironment components affecting tumor growth.

The Role of the Microenvironment – Models for the Study of Melanoma

“…(mean) (Speroni et al, 2009a). Importantly the hosts of tumors in the dorsal region of the foot had a poor survival compared to the hosts of flank tumors (Speroni et al, 2009a). Our results clearly show that, even though the tumor cell line was the same, when injected in the mice, these cells originate remarkably different tumors which malignancy is dependent on the anatomic site of the skin.…”

“…Conversely, lung metastases were observed in 100% hosts bearing melanoma tumors in the dorsal region of the foot that survived beyond day 14 p.i. (mean) (Speroni et al, 2009a). Importantly the hosts of tumors in the dorsal region of the foot had a poor survival compared to the hosts of flank tumors (Speroni et al, 2009a).…”

“…Seven days after immunization with SRBC, sera was obtained and antibody titer was analyzed by hemagglutination assay. We found that a significantly higher antibody titer was obtained when SRBC were inoculated in the dorsal region of the foot than in the flank (Speroni et al, 2009a). Since different levels of inflammatory and immune response were observed, we further evaluated the growth of B16F0 melanoma in both anatomic sites.…”

“…In a previous work we investigated whether the dermis of a different anatomical site of mice would offer different characteristics than those of the flank. Thus, we chose the dorsal region of the foot and compared it to the flank in terms of cellular influx and reactivity (Speroni et al, 2009a). We further compared the acute and chronic inflammatory response in the selected areas of the skin in order to gain better understanding of the reactivity of both anatomic sites.…”

Defining microenvironments within mouse models that enhance tumor aggressiveness

“…7 Here the mouse dorsal foot is compared to the more conventional flank subcutaneous site using syngeneic mouse tumors derived from MC-C fibrosarcoma and B16F0 melanoma cell lines. For both tumors, the dorsal foot microenvironment conferred a greater inflammatory response and decreased local growth relative to the less reactive subcutaneous site.…”