Thus, the identification of SPP1 as an abundant TAM-secreted factor in cancer, coupled with the pro-tumor impact of SPP1, suggests that inhibiting SPP1 at transcriptional or protein level, blocking the interaction between SPP1+ TAMs and cancer cells through targeting SPP1 and CD44, may be an effective clinical strategy for tumor growth and metastasis inhibition. This evidence concerns the gene CD44 and cancer.