Locally Increased Metastatie Efficiency as a Reason for Preferential Metastasis of Solid Tumors to Lymph Nodes

Abstract

Metastases from solid tumors to lymph nodes do not portend as poor a prognosis as metastases to other sites. The authors wished to determine whether specific subpopulations of cells metastasized to lymph nodes and whether they have different properties than cells metastatic to visceral sites. Repetitive selection for "spontaneous" metastases of a B16 melanoma to either lung or lymph node increased the incidence of lymph node metastases. Cells derived from pulmonary and lymph node metastases were assayed for their ability to adhere to cryostat sections of lung and lymph node and respond to target organ-conditioned media in serum-free conditions. Both cell types were four times more adherent to lymph node than lung, and consistently attached to the hilar and subcapsular sinuses. Attachment of cells derived from pulmonary metastases to either tissue was threefold greater than that of cells derived from nodal metastases. Lung-conditioned media stimulated proliferation of both cell types, and transiently induced differentiated morphology in cells derived from lymph node metastases, but not in cells from pulmonary metastases. Neither effect was found in lymph-node-conditioned medium. These results suggest that cells metastasize to lymph nodes preferentially not because of a specific predilection for lymph node, but because it is an easy site to colonize. Adhesive interactions in the lymph node rather than trophic ones appear to account for this effect. Cells metastatic to lymph node may be less "malignant" than cells metastatic to visceral sites because less has been required for them to succeed as a metastatic focus.

Granulocyte‐macrophage colony‐stimulating factor stimulates the metastatic properties of lewis lung carcinoma cells through a protein kinase a signal‐transduction pathway

“…Our results show that, in the presence of rGM-CSF, the capacity of metastatic LLC tumor cells to migrate, invade through basement membrane and adhere to lung tissue was increased. The enhanced adherence to lung tissue did not display an anatomical preference, consistent with results previously shown for lung-metastasizing B16 melanoma cells (Whalen and Sharif, 1992). In addition, the capacity of tumor cells to form experimental metastases after in vitro treatment with rGM-CSF was increased.…”

Pivotal Role of CXCR3 in Melanoma Cell Metastasis to Lymph Nodes

“…Mouse melanoma cell line B16F10 provides a convenient transplantable model that is metastatic to LNs in the syngeneic host, C57BL/6 (14). We first determined expression of various chemokine receptors (CCR1-CCR10, CXCR2-CXCR5, XCR1, and CX 3 CR1) in B16F10 cells by RT-PCR.…”

What can we learn from the phenomenon of preferential lymph node metastasis in carcinoma?

“…In later stages, lymphatics and lymph nodes become clogged with tumor cells and the lymph node can no longer filter the cells. The node becomes an independent tumor and is quite capable of inducing subsequent metastases if it is removed and transplanted to another animal [7]. Although lymph node size is often indicative of infiltration by tumor cells, this is not invariably true.…”

“…For example, there is some evidence that increased tumor cell attachment in the lymph nodes rather than growth stimulation by a cytokine-rich environment is at least partly responsible for the pattern of preferential lymph node metastasis [7]. Promotion of cell-cell adhesive interactions between T cells, B cells, and professional APCs appears to be a crucial function of the lymph node.…”