Tumor Cells and Tumor-Associated Macrophages: Secreted Proteins as Potential Targets for Therapy

Inflammatory pathways, meant to defend the organism against infection and injury, as a byproduct, can promote an environment which favors tumor growth and metastasis. Tumor-associated macrophages (TAMs), which constitute a significant part of the tumor-infiltrating immune cells, have been linked to the growth, angiogenesis, and metastasis of a variety of cancers, most likely through polarization of TAMs to the M2 (alternative) phenotype. The interaction between tumor cells and macrophages provides opportunities for therapy. This paper will discuss secreted proteins as targets for intervention.

Recurrence

Recurrent phenotypes are similar or identical phenotypic traits with discontinuous phylogenetic distributions, which owe their similarity to common ancestry (homology). A recurrent trait may be found as a fixed trait, as an alternative phenotype (one morph of a polymorphism or polyphenism), or as a low-frequency developmental anomaly. Recurrence, then, is the phyletically disjunct appearance of homologous traits. An example is the repeated evolution of larviform (paedomorphic) adults in salamanders. The larviform morph is characterized by retention in the reproductive stage of homologous larval traits such as external gills and a tail. This has involved changes at various points in the hormonal mechanism that controls metamorphosis in all salamanders (chapter 25), perhaps under selection for accelerated reproduction in stressful environments (Whiteman, 1994). As is characteristic of recurrent phenotypes, the occurrence of the reproductive larviform adult morph varies in frequency from one species of salamander to another: it can be absent, an anomaly (<5% of population), a common (>5%) alternative to complete metamorphosis, or a predominant or fixed form. Even within the genus Ambystoma, the unmetamorphosed larviform adult occurs as an occasional anomaly in some populations, as a facultatively expressed alternative phenotype in others (e.g., A. tigrinum) and as a fixed form in others (e.g., A. dumerilii; Collins et al., 1993). All atavisms and reversions (see chapter 12) are examples of recurrence. Discontinuity of expression is expected in combinatorial evolution, where traits are turned off and on and expressed in different combinations due to regulatory change. The growing evidence of homoplasy in phylogenetic studies is important evidence that combinatorial evolution occurs and that homoplasy itself is worthy of study, not just a source of “noise” in cladistics (Wake, 1996a). Homoplasy has been defined as “possession by two or more taxa of a character derived not from the nearest common ancestor but through convergence, parallelism, or reversal”. More simply, homoplasy is the recurrence of similarity in evolution (Sanderson and Hufford, 1996).